Immunology Today, Vol. 1 I, No. 1 1990

and should be particularly useful when combined with single-cell in- vestigations of cytol, ine secretory properties.

Immunodeficiency Since diarrhoea and weight loss are

so characteristic of acquired immune deficiency syndrome (AIDS), it is per- haps ::,urprising that only recently has there been careful investigation of the gastrointestinal tract of affected patienLs. Human immunodeficiency virus (HIV) infection of human intesti- nal mononuclear cells (C. Fiocchi, Cleveland) and of intestinal epi- thelium (M.F. Kagnoff, San Diego)

have been demonstrated and it is clear that the changes in the intestinal epithelium are subtly differ- ent from those of other infectious and inflammatory diseases of the gut (M. Zeitz0 Berlin; A.G. Cummins, Adela!de).

This report has concentrated al- most entirely on the gastrointestinal tract since that is mv ,~wn interest, but paoers relevant to other mucosal surfaces including the eye, the nose, the genital tract, the urinary tract and respiratory system were abundant; two interesting papers demonstrated possible effects of cigarette smoking on mucosal immunology (G.F. Cope,

Leeds; J .R. Barton, Edinburgh). J. Holmgren and A.M. Svennerhoim (Gothenburg) separately presented details of progress in the develop- ment and application of oral vac- cines; the oral cholera vaccine containing cholera B sub-unit cross- reacts immunologically with E. coil heat labile enterotoxin (LT) and has been shown to afford significant pro- tection against diarrhoea caused by LT producing enterotoxigenic E. coil (ETEC) in humans.

Anne Ferguson is at the Department of Medi- cine, Western General Hospital, Edinbu~h EH4 2XU, UK.

The WHO Nomenclature Committee for Factors of the HLA System t met during the Seventh Intematin. nal Congress of Im- munology to consider additions to pre- vious reports. Here new data on DNA sequences of alleles and of three new loci are presented and names of new a/le!~s and led defined by nucleotide or inferred amino acid sequences are given.

Introouction by Julia Bodmer A generally accepted and univer-

sally used system of nomenclature is an essentia! tool in any area of study. This is particularly so in an area such

+,,...+,,.4,, ..~ the ~ . . . . . . . ~ + "

Nomenclature for factor; of the HLA system, 1989

from Julia G. Bodmer, Steven G.E. Marsh and Ekkehard Albert*

compatibility system (HLA), which consists of a cluster of genes on chromosome 6 whose level of polymorphism is probably un- matched in any so far defined human

gene cluster. The close collaboration of the originally small but now enor- mous number of laboratories world- wide in - series of International Histocompatibility Workshops Iqas

I I I l , l l l : I , I~CI111~'3 IUI L jEI I I : ", h i I.IIE I llJ'~ IL--LjIUII

*The following committee members were in- volved in preparing this report: J.G. Bodmer, Imperial Cancer Research Fund, London, UK (Ra[porteur); E. Albert, Polictinic for Children, Unive:sity of Munich, FRG (Chairman); W.F. 3odmer, !mperial Cancer Research Fund, London, UK; B. iDupont, Sloan-Kettering In- stitute for Cancer Research, New York, USA; B. Macl, University of Geneva, Geneva, Switzer- land; W.R. Mayr, Rheinisch-Westf~lische Tech- nische Hochschule, Aachen, FRG; 1. Sasasuki, Kyushu University Fukuoka, Japan; G.M.Th. Schreuder, University Hospital, Leiden, The Netherlands; J.L. Strominger, Harvard Univer- sity, Cambridge, Massachusetts, USA; A. Svejgaard, State urwersi b' Hospital, Copen- hagen, Denmark; P.I. Terasaki, University of California, Los Angeles, California, USA. Co-opted members of the committee: S.G.E. Marsh, Imperial Cancer Research Fund, London, UK; P. Parham, Stanford University School of Medicine, Stanford, California, USA; H.A. Erlich, Cetus Corporation, Emeryviile, California, USA.

tThe WHO Nomenclature Committee for fac- tors of the HLA System met on 1 August 1989 during the Seventh International Congress of Imm,Jnology in Berlin.

Name Previous Molecular characteristics equivalents

HLA-A HLA-B HLA-C - HLA-E E, '6.2' HLA-F F, '5.4' HLA-G G, '6.0' HLA-DRA DR~ HLA-DRB1 DR131, DR1B

HLA-DRB2 DR1311 HLA-DRB3 DR~III, DR3B

HLA-DRB4 DR131V, DR4B HLA-[DRB5 DR13111 HLA-DQA1 DQc~I, DQIA HLA-DQB1 DQ131, DQ1B HI.A-DQA2 DXo~, DQ2A HLA-DOB2 DX13, DQ2B H~.-DOB DO13 HLA-DNA DZc~, DOs HLA-DPAI DP~I, DPIA H~-DPBI DPI31, DPIB HLA-DPA2 DPo2, DP2A HLA-DPB2 DP132, DP2B

class I ~ chain class I ~ chain class I ~ chain associated with class 16.2 kb H!ndlll fragment associated with class 1 5.4 kb Hindlll fragment associated with class! 60 kb Hindlll fragment DR o~ chain DR 131 chain determining specificities DR1, DR3, DR4, DR5 etc. pseudogene with DR-13-1ike sequences DR 133 chain determining DRw52 and Dw24, Dw25, Dw26 specificit~es DR 134 chain determining DRw53 DR 135 chain found ~n DR2 haplotyp,:s DQ a ck, ai:, as expressed DQ 13 chain as expressed DQ s-chain-related sequence, not known to be expressed DQ 13-chain-related sequence, not known to be expressed DO 13 chain DN ~ chain DP ~ chain as e~,pressed DP 13 chain as expressed D? o~-chain-related pseudogene DP !3-chain-related pseudogene

Refs for new genes

4,5 4,5,6

3 (~) 1990. Elsevier Science Publishers Ltd. UK 0167 4919/89/$02 CO

Immunology Today, Vol. 11. No. 1 1990

enabled the development of Hba, no- menclature in an orderly and ac- cepted manner. It has been the policy that only the WHO Nomenclature Committee has the authority to as- sign official names to factors of the HLA system and that local names, assigned by a laboratory to a newly defined specificity, should not re- semble offioal nomenclature in such a way as to pre-empt the official naming cf the specificity.

Since 1967, reports of the HLA Nomeqclature Committee, under the auspices of the World Health Organ- ization, have been published in con- junction with, and based very largely on, the results of the immediately preceding International Histocom- patibility Workshop. This continued to be the practice up to and including the eighth report published in con- junction with the 1987 Workshop held in Princeton, New Jersey ~2. In these reports the main concerns were the establishment of the principles of nomenclature, which have evolved with the increasing knowledge of the system, especially at the molecular level, and the naming of specificities which had been identified using a common set of reagents in the im- mediately preceding workshop.

In the eighth report, guidelines were laid down for the namin'~ of genes ano alleles identified by-nu- cleotide sequencing and a new gene and several aiieie sequences were so named. Since the eighth report was written many new sequences have been published. As the naming of these does not depend on the use of common reagents, as is the case for serologically and cellularly defined specificities, it was decided to issue a nomenclature report indepen- dently of a Histocompatibility Work- shop. This report therefore confines itself to the naming of genes and alleles identified by sequencing. The naming of serologically and cellularly defined specificities will continue to be reported immediaLely after International Histocompatibility Work- shops.

Nomenclature for factors of the HLA system. 1989

The WHO Nomenclature Commit- tee for Factors of the HLA System met during the Seventh International Congress of Immunology in Berlin in August 1989 to consider additions to the previous report on Nomenclature for Factors of the HLA System, 1987

4

Table 2. Designations of HLA-A. -B and -C alleles

HLA HLA Previous Individual or c.~,ll line from which References alleles a specificity equivalents the sequence was derived

A*0101 A1 - LCL721 8 A*0201 A2 A2.1 LCL72 ,, JY, GM637 3,9,10 A*0202 A2 A2.2F M7. 11 A*0203 A2 A2.3 DKI 11,12 A*020I A2 - AZL 13 A*0205 A2 A2.2Y WT49, AM 12 A*0206 A2 A2.4a CLA, T7527 14,15,16 A*0207 A2 A2.4b KNE 17 A*0208 A2 A2.4c KLO 18 A*0209 A2 A2-OZB OZB 19 A'0210 A2 A2-LEE XLI-ND 20 A*0301 A3 A3.1 JG b 21,22 A*0302 A3 A3.2 E IB2 23 A'1101 A11 A11E CJO 24 A'2401 A24 (9) - JG b 22,25 A'2501 A25 (10) - BM92 3 A'2601 A26 (10) - GM637, 02BN5 10,26 A'2901 A29 (w19) - JOE 27 A'3001 A30 (w19) A30.3 LBF 28 A'3101 A31 (w19) - JHAF 28 A'3201 A32 (w!9) - AM 29 A'3301 Aw33 (w19) Aw33.1 JOE 28 A'6801 Aw68 (28) Aw68.1 LB 30 A'6802 Aw68 (28) Aw68.2 PA,TO 12 A'6901 Aw69 (28) - IDF,ZM,BJ 30

B*0701 B7 B7.: CF 31 B*0702 37 B7.2 JY 3,32,33 B*0801 B8 - LCL721,MF 8,34 B'1301 B13 B13.1 HE 35 B'1302 B13 BI~., LBF,TO 36,37 B'1401 B14 - MRWC 8 B'1402 Bw65(14) - BB 8 B'1501 Bw62(15) - MF 34 B'1801 B18 - SGAR

aAllele names given in bold type were assigned previously.

(Refs I, 2). This report, taking into ac:ount only new data on DNA se- quences of alleles and of three new loci, therefore concerns only +he naming of new alleles and loci de- fined by nucleotide or inferred amino acid sequences. It should, therefore, be considered as a supplement to, and used in conjunction wi th the 1987 report cited above.

Thus Table I - Names for genes in the HLA region - includes the new genes named for the first time in this report and updates Table I of the 1987 report. Table 2 - Designations of HI_A-A, -B and -C alleles- updates Table 3 of the 1987 report, and Tables 3, 4 and 5 - Designations of the HLA-DR, -DQ and -DP alleles -

update Table 4 of the 193i report. Tables 5-9 and comments of the 1987 report relating to serological and cellular determinants remain un- changed and will be considered at a later meeting of the Nomenclature Committee.

The naming of the new genes and alleles listed in Tables 1-5 of this report follows the principles stated in the 1987 report.

Criteria for acceptance of a sequence in naming a gene or allele

The criteria for acceptance of a sequence, laid down in the 1987 re- port, included depositing in publicly accessible repositories or databases: (1) the clone(s) from which the se-

Immunology Today, Vol. 11, No. 1 1990

HLA HLA . Previous lndiwdual or cell line from which References alleles a specificity equivalents the sequence was derived

B'2701 B27 27f LH 38 B'2702 B27 27e,27K,B27.2 BRUG 39 B'2703 B27 27d,27J CH (CH!) c 40,41 B'2704 B27 27b,27C,B27.3 WEWAK 1 42 B'2705 B27 27a,27W, B27.1 BRUG,CD b 39,43 B'2706 B27 27D,B27.4 LIE B'3501 B35 - HS b 45 B'3701 B37 - KASO,MG 3 B'3801 B38(16) B16.1 Z b 46 B'3901 B39(16) B16.2 S b 46 B'4001 Bw60(40) - LB 47 B'4002 B40 B40* SWEIG 48 B'4101 Bw41 - SGAR 8 3"4201 Bw42 - BB 8 3"4401 Ba4(12) B44.1 BAU 49 t'4492 B44(12) B44.2 FMB 8 ,3"4601 Bw46 - T7527 15,16 B'4701 Bw47 - PLH 36 B'4901 B49(21) - AM t6 B'5101 B51(5) - LKT-2,TO,BM92 3,37 B~5201 Bw52(5) - MT b 37 B'5701 Bw57(17) - WlN,MOC 3 B'5801 Bw58(17) - WT49 50

Cw*0101 Cwl - BRUG 51 Cw*0201 C,v2 Cw2.1 BRUG 51 Cw*0202 Cw2 Cw2.2 MVL 8 Cw*0301 Cw3 - JG b 22,52 Cw*0501 Cw5 - QBL 53 Cw*0601 Cw6 - JOE 54 Cw*0701 Cw7 - MF 34 Cw'1101 Cw11 - T7527 15,16 Cw~1201 - Cx52 AKIBA 55 Cw~1301 - CwBL18 TCC 53 Cw'1401 - Cb-1 MT b 56

blndividual from which sequence was derived. cCell line is also known by alternative name.

que:lce was derived; (2) the cell source(s) from which the clone(s) was derived; and (3) the nucleotide se- quence or, if this is not available, the amino acid sequence. Publication of a sequence or acceptance by a public DNA database facility, such as EMBL or GENBANK, is considered sufficient confirmation of the validity of a sequence.

The importance of naming and having available on deposit an appro- priate cell line is again emphasized. This is the most secure wa~, to guar- antee the possibility of confin'ning and reproducing a sequence. The se- quence name can thus be related to the cell source listed, minimizing any problems due to sequence errors,

since eventually the corre'_~ sequence for the cell retains the allele or gene name originally given. If, due to er- rors, names are given to sequences which cannot later be con, irmed, those names will be dropped. In order to minimize the risk of error, it is recommended that, when sequenc- ing is carried out on individual clones derived from polymerase chain re- action (PCR) amplification, between three and six clones should be sequenced 3.

Following the !987 report, allele names are, for the time being, based on amino acid sequences. Names given on the basis of partial or amino acid sequences which prove to show further variation when a complete

nucleotide sequence is available, will, as suggested in 1987, be subdivided to indicate their relationship to the original incomplete sequence; f,~- example variants of DRB1 "0301 may be named DRB1 "0301 1, 03012 etc.

New genes Table 1 includes three newly

named genes - two class I genes and one class II gene. The two class I genes are HLA-F and HLA-G which map telomeric to HLA-A, HLA-F (Refs 4, 5) being defined by a 5.4 kb Hindlll fragment detected by a class I probe and HLA-G (Refs 4-6) by a 6.0 kb Hindlll fragment. The order of these two genes, which map physically closely togethe,, is not yet estab- lished. One new class II gene has been named, DRB5. The alleles coded at this locus are four recently identified second DR [3 chains associated with DR2 specificities, two associated with DRw15 and two with DRw16 (as shown in Table 3). Genomic analysis 7 shows that DRB5 maps in a position similar to the DRB3 gene found in other hapiotvpes. The DRB5 se- quences appear to be closely related to DRB1 sequences, in that they are as similar to DRB1 alleles as DRB1 alleles are to each other, suggesting that DRB5 may be a relatively recent duplicate of DRB1. The DRB5 se- quences are as different from DRB3 and DRB4 as are those of DRB 1_

HI.A-A, -B and -C alleles Additions to the list of officially

designated HLA-A, -B and -C alleles are based on the publication of a large number of new DNA se- quences. Table 2 shows the complete list of class I HLA alleles. In the first column, allele names given in bold type were assigned in the 1987 Nomenclature Report ~.2, alleles as- signed at a,ld after the 1989 nomenclature meeting are given in normal type. The second column indi- cates the associated serological speci- ficity, with any previous Ioca! ~.;: rues in the third column. ThE faugh column gives a new piece of iqfor- mation, the name of the individual or cell line from which the sequence was derived. Either the cell name or, in the absence of a suitable cell line, the availability of clones from which a sequence is derived, are now con- sidered essential before a sequence can be given an official name.

References to the publications in

fe t.res Immunology Today, Vol. 11, No. 1 1990

Table 3. Designations of HI_A-DR alleles

HLA HLA-DR HLA-D-assJciated Previous alleles a specificities (T-cell-defined) equivalents

specificities

oR81-oIoI DRI Dwl - DRBI*OI02 DR1 Dw20 DRI-NASC DRBI*OI03 DR'BR' Dw'BON' DRI-CETUS DRBI * 1501 DRwl 5(2 ~. Dw2 DR2B Dw2 DRBl*1502 DRw15(2) Dw12 DR2B Dw12 DRBI* 1601 DIe, v16(2) Dw21 DR2B Dw21 DRBI* 1602 Dlb~l 6(2) Dw22 DR2B Dw22 DR81"0301 DRwl 7(3) Dw3 - DRB I *0302 DRwl 8(3) Dw'RSH' - D1~1"0401 DR4 Dw4 - DilBl*0402 DR4 Dw 10 - ORB1"044)3 DR,: Dwl 3 DR4, Dwl 3A, 13.1 DRBl*0404 DR4 Dw! 4 DR4 Dwl 4A, 14.1 DRBl*0405 DR4 Dw 15 -

DRB 1 *0406 DR4 Dw'KT2' -

DRBI*0407 DR4 Dw13 DR4 Dwl3B, 13.2 DRB1*0408 DR4 D w 1 4 DR4-CETUS,Dw14B,

14.2 DRBI*1101 DRwl 1(5) Dw5 DRw11.1 DRB1 *1102 DRwl 1(5) Dw'JVM' DRwl 1.2 DRBI "1103 DRwl 1(5) - DRwl 1.3 DRB1 "1104 DRwl I(5) Dw'FS' - DRB1*1201 DRw12(5) Dw'DB6' DR81* 1301 DRw13(w6) Dw18 DRBI* 1302 ORw13(w6) Dwl 9 DRBI* 1303 DRw13(w6) Dw'HAG' DRB1*1401 DRw14(w6) Dw9

DR81"1402 D Rw14(w6) Dw16 DRBI*0701 DR7 Dw17 DRBl*0702 DR7 Dw'DBI' DRB 1 "0801 DRw8 Dw8. i DRBi*~02 DRw8 Dw8.2 DRB 1 *0803 DRw8 Dw8.3 DRB 1"0901 DR9 Dw23 DRB1*1001 DRwI0 -

DRw6a I DRw6c I

DRw6b I, D RB 1 * 1402 [70] DRB1*1401170]

DRw8-SPL DRw8-TAB

Cell line from which References sequence was derived

LG2 - 57 NASC 58 PAl, BG 59,60 PGF 57,61 BGE, DHO 61,62 AZH, MN-2 61,62 REM (RML) b 63 RAJI,AVL,WT49 57,64,65 2041 66 GM3103,WT51 67 FS 67 SSTO 68 BIN40,LS40 67,68 KT3 67 KT2 69 JHF 70-72 M36, RAt 60,70,72

SWEIG 73 JVM 57 UA-S2 74 FPA (FPF) b 75 HERLUFF 76 HHKB,APD 57,65 WT46 77 HAG 78 t 4/w6, TEM 65,79

AMALA (LIA,AZL) b 79 BURKHARDT 80,81 LBF 57 MADUPA 57 SPL 82 TAB089 60 ISK,DKB 57,81 RAJI 58,64

BRB*OIO1 DRw52a Dw24 DR3 !II, DRw6a I!! DRB*0201 DRw52b Dw25 DRw6b III DRB3*0202 DRw52b Dw25 pDR51B.3 DRB3*0301 DRw52c =,v26 -

AVL, HHKB 65 4/w6,WT49 57,83 SWEIG 84 WT46 85

I)RB4"0101 DRw53 Dw4,Dw10,Dw13, Dw 14,Dw 15,Dwl 7, Dw23

LBF,DKB,BURKHARDT, 57,67,81,86,87 KT3,FS,PRIESS,MANN

DRB5*0101 DRw15(2) DRB5*0102 DRw15(2) DRB5*0201 DRw16(2) DRB5*0202 DRw16(2)

Dw2 DR2A Dw2 Dw12 DR2A Dw12 Dw21 DR2A Dw2 ! Dw22 DF,2A Dw22

PGF 57,61 BGE, DHO 61,62 AZH, MN-2 61,62 REM (RML) ~ 63

aAllele names given in bold type were assigned bCell line is also known by alternative name. tKenter et al. (pers. commun.).

previously.

which these sequences were re- ported are given. Where possible more than one reference to a se- quence is given to document its confirmation

HLA-A alleles Four HLA-A locus alleles related to

the HLA-A2 specificity had been named in the 1987 report. This report lists ~lenty-one new A locus alleles,

of which six are for further HLA-A2 variants. It should be noted that the first two A2 alleles have been re- assigned: A*O201 is now the com- mon A2 allele previously known as

Immunology loday, Vol. 1 I, No. 1 1990

Table 4. Designations of HLA-DQ alleles

!

i-ILA HLA-DQ alleles specificities

DQ~1*0101

HLA-D- Previous associated equivalents (T-cell-defined) specificities

Cell line References

Dwl,w9 DQA 1.1, 1.9 LG2,BML 88-91 ! DQAI "0102 DQAI "0103

DQAI*0201 DQAI*0301

DQAI*0401 DQAI*0501 DQAI*0601

Dw2,w21,w19 Dw18,w12,w8, Dw'FS' Dw7,wl 1 Dw4,w10,w13, w14, w15,w23 Dw8,Dw'RSH' Dw3,w5,w22 Dw8

DQA 1.2, 1.19, 1.AZH DQA 1.3, 1.18, DRw8-DQwl

DO~ 2, 37 DOA ~, "~1, 3.2, DR9-DQw3

DQA 4.2, 3.8 DQA 4.1, 2, DQA1 *0202[70] DQA 4.3, DQA1*0302170]

DQBI*0501 DQw5(wl) Dwl DQB 1.1, DRwl0-DQwl.1, DQB1 "0101 [701

DQB1*0502 DQw5(wl) Dw21 nOB 1.2, 12t, DQB1*0102170] DQB1 *0503 DQw5(wl) Dw9 DQB 1.3, 1.9, DQB1 "0103170] D~31"0601 DQw6(wl) Ow12,w8 DQB 1.4, 1.12, DQB1*0104170] DQB1 *0602 DQw6(wl) Dw2 DQB 1.5, 1.2, DQ81 "0105170] DQ81"0603 DQw6(wl) Dw18,Dw'FS' DQB 1.6, 1.18, DQB1*0106170] DQB1*0604 DQw6(wl) Dw19 DQB 1.7, 1.19, DQB1*0107170] DQ81*020i DQw2 Dw3,w7 DQB 2

DQB1*0301 DQw7(w3) Dw4,w5,w8, w13

DQB1*0302 DQw8(w3) Dw4,w10,w13, w14

DQB1 *0303 DQw9(w3) Dw23,w11 DQ81*0401 DQw4 Dw15 DQB1 *0402 DQw4 Dw8,Dw'RSH'

DQB 3.1

DQB 3.2

DQB 3.3 DQB 4.1, Wa DQB 4.2, Wa

PGF,LB,CMCC,AZH,WT46 88,90-92 APD,TAB,FPF,WVB 89-91

LGIO,BEI 90,91,93 JY, MMCC,NIN,DKB,ISK 88,90-92,

94,95 ARC,2041, MADURA 90,91,96 RNI, CMC C,SWEIG 88,91,92,97 LUY 91

LG2,45.1,BML, MVL 90,91,98,99

AZH 90,91,100 HUI29,HU128,VM'[52 90,91 DQBS4,BGE,TAB 90,9i,100,101 DOBS5,PGF 90,91,100 WVB,APD,FPF 90,91 CMCC,DAUDI 88,90,91 WT49,QBL, BURKHARDT,CMCC 80,88,90,91,

102 SWEIG,DQB37,NIN,JHA, 90,91,103 LUY,JGL,JME DCB4,FS,BIN40,3102 66,90,91,104

KOZ, DKB 90,91 KT3 67,91 ARC,OLN,2041 90,91,96

A2.1 and A*0202 is the variant pre- viously known as A2.2F.

HLA-B alleles Eight HLA-B locus alleles, of which

two were B7 variants and six B27 variants, were listed in 1987. To these, 24 new allele names have now been added. In some cases 'split' anti- gen names have been used as the basis for naming alleles, for example B51- and Bw52-related sequences are given allele names of B'5101 and B'5201 respectively. In other cases, where the sequence difference be- tween two 'splits' is minimal or where a sequence comes from a broad anti- gen and not a defined split, the broad antigen name was used as the basis. This was the case, for example, for B14-related alleles B'1401 and B'1402, as well as for B'4001 and B'4002 and B* 1501.

HLA-C alleles HLA-C locus alleles were named for

the first time. Eight of the 11 named relate to serologically defined C locus

antigens. The ninth, designated Cw'1201 i~ a C locus allele corres- ponding to part of the Cw 'blank' and is generally found in close association with Bw52. This allele is defined by its DNA sequence and has not so far been identified serologically. The name HLA-Cw12 ,viii be reserved for the corresponding serological speci- ficity if it is identi.ied, bul will in any c3se not be useci f : r any other HLA-C locus antigen. The, same is true for Cw* 1301 and Cw* 1401, which also so far have no corresponding sero- logical specificides.

HI.A-DR, -DQ and -DP alleles New designations for HLA-DRB1,

-ORB3, -DRB5, -DQA1, -DQB1, -DPA1 and -DPB1 alleles are given in Tables 3, 4 and 5. Five DRB1 alleles, three DRB3 alleles and one DRB4 al- lele were named in the 1987 report. In this report, 29 new DRB1 alleles, one new DRB3 allele and four new DRB5 alleles are named. As in the naming of the class I alleles, the choice of the broad or the split anti-

gen as the basls for naming alleles depended mainly on the degree of sequence similarity between alleles and also took into account names in general use.

DRB locus alleles At the DRB 1 locus the DR2-related

alleles were named after the DRwi5 and DRw16 splits; DRwl i-, DRw12-, DRw13- and DRw14-related alleles were also named after the splits; whereas DR3-related sequences were listed as DRBI*O301 and DRB1 *0302 respectively.

The Dw type listed in column three of the table does not imply that the Dw type is coded by this allele exclus- ive!y, but is intended merely as a guide to the Dw type usually, but not necessarily always, associated with a particular allele.

The one new allele named at the DRB3 locus, DRB3*0202 is thus usually found in cells typing as Dw25. The four new alleles listed at the DRB5 locus are, as discussed above, found in association with the DRwl 5

TIMe f, 0~ignations of HLA-DI alleles

HLA Assooated Previous Cell lir.e aletes HL~-DP equivalems

speoficities

References

DPAI'0!01 - LB14/LB24, DPA1 LB 92,105,106 DPAl'0102 - pSB0v318 LG2 105 DPAI*0103 - DPw4Q1 BO 107 DPAI*0201 - DPA2, pDAoA3B DAUDI, AKIBA 105,106

DPBI'0101 DPwl DPB1 LUY 106 DP31"0201 D~2 DPB2.1 JY, LB, 451 106,108-110 DPB1*0202 DPw2 DPB2.2 QBL, MANN 106 DP81*0301 5Pw3 DPB3 SLE,PRIESS 106,109 DPBI"0401 DI:M'4 DPB4.1, DPw4a HHKB,BO,PRtESS 106,109,111-113 DP8t*0402 DPw4 DPB4.2, DIM'4b APD,BURKHARDT 106,114 DPB 1 "0501 DPw5 DPB5 HAS 106 DPB1 "0601 DPw6 DPB6 JMOS 106 DP81*0801 - DPB8 PIAZ 106 DP81*0901 DP'Cp63' DPB9 TOK 106 DP81"1001 - DPB10 BM21 106 DPBI*1101 - DPBII CRK 106 DP81*1301 - DPB13 NB 115 DP81*1401 - DPB14 8268 115 DPBl*1501 - DPB15 PLH 115 DP81*1601 - DPB16 JRA 115 DPBl*1701 - DPB17 JRAB 115 DPB1*180t - DPB18 JCA 115 DPB1*1901 - DPB19 CB6B 115

and DRw16 antigens coded for by DRB1*1501 etc. at the DRB1 locus. These alleles are usually found in as- sociation with the Dw types listed.

oO ioo Table 4 lists eight DQA1 alleles and

13 DQB1 alleles which were named for the first time.

DOA1 alleles. The fact that the ~hree DQA1 alleles most often associated with the DQwl antigen were very similar to each other in sequence was the basis for naming them DQAI*O101, DQAI*0102 and DQA1*0103 respectively. The five other DQA sequences do not have particular sequence features in com- mon with each other, nor were they exclusively associated with a particu- lar DQB1 ailele. It was therefore decided to name them sequen- tially DQA1*0201, DQA1*0301, DQA1 "0401, DQA1 "0501 and DQA1*0601. It was also considered inappropriate to name DQA1 alleles on the basis of their most common DQB 1 associations, since such associ- ations may not be the same in differ- ent populations.

DQBi alleles. The DQw5 and DQw6 serological splits of DQwl were

used as the basis for naming DQB1 allele sequences related to these specificities. Thus, three DQB1 se- quences related to DQw5 and four

' ÷ '~ to DQw6 were named re,a,e,. DQB1*0501 and DQB1*0601 etc. Only one DQw2 sequenc~ has been named, for DQw3-related sequences it was decided to use the broad antigen name as the basis for naming the three alleles since the distinction between two of the serological splits, namely DQw8 and DQw9, has been found difficult to identify and there was no obvious subdivision of the allele sequences. Two DQw~- associated sequences were nameo DQB1*0401 and DQB1*0402 re- spectively.

DPA 1 and DPB 1 alleles Table 5 lists the four DPA1 alleles

and 17 DPB1 alleles which have been named. The naming of the DP alleles is based on their patterns of sequence similarity and follows that given to the published sequences. Six of the DPB1 alleles are associated with the officially identified DP types, and one with Cp63, assigned previously by cellular methods, as shown in column two. Gaps are left for DPBI*0701 and DPBI*I ~'I~,, pending confir- mation of the sequences.

Immunology Today; Vol. 1 I, No. 7 1990

Further assignment of allele names Given the rapid rate of production

and publication of DNA sequences for HLA alleles and genes, it was dec!ded that the Nomenclature Committee should aim to meet an- nually and also consider additions to nomenclature throughout the year so that official names can be given as quickly as possible. As soon as a sequence is accepted for publication or deposited in a public database, it should also be communicated to the Chairman of the Nomenclature Committee. The Nomenclature Com- mittee will then assign the sequence an official or provisional HLA allele name and will submit it in computer- readable form to an international DNA sequence bank who will give the sequence a unique accession number. If possible the HLA allele name and the accession number should be quoted in the published report of the sequence. In this way sequences can be made available publicly as soon as possible, together with their official designation and avoiding the confusion that can otherwise result when nomenclature decisions are delayed.

New sequences should be communicated to E. Albert (Chairman of the committee) to receive official names. Address: Pettenkofer Street 8A,

r~_Q(~£~ ~A~"~n~h~ 2 , rDF'_

Telephone no: 00-49-89-5160-5713 Fax no: 00-49-89-532-8141

Julia Bodmer and Steven Marsh are at the Imperial Cancer Research Fund, London, UK and Ekkehard Albert is at the Pohclinic for Children, University of Munich, FRG.

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Immunology Today, Vol. I 1, No. 1 1990

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-FgVfg $ Immunology Today, Vol. 11, No. 1 1990

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intrasplenic immunization with minute ~ere are two ways to raise antibodies to minute amounts of immunogen. The first is in-vitro immunization I in which the immunogen is presented to a spleen cell culture and about a week later cell fusion for hybridoma production is attempted. The second, and the subject of this review, is intrasplenic immunization 2, in which the immunogen is deposited into the

' --'~ ~- . . . . . . . . . . . . . . . f g wing ~ ,~ , , ,,oou~ a, lu u~e d,,nd~ ~etr ~aKes care 0 ro the spleen cells. Both of these techniques are appropriate when only small amounts of immunogen are available. Intrasplenic immu- nization, however, requires less laboratory work and there is a decreased risk of contamination, o#en a problem with hy- bridoma cukures 3. The experience of intrasplenic immunization shows that it is the method of choice for immunization with nanogram am~un~ of ~mmunogen. A successful outcc.,~e, however, requires that the immunogen is immobJized on a carrier. This rewew by Ove Nilsson and Anders Larsson will focus on the various types of matrix which can be used as cc, rriers and on the procedures for transferring these carriers into the

spleen tissue.

Intrasplenic immunization was introduced by Nilsson et al. ~. Estimation of the sensitivity of the intrasplenic immu- nizatien technique si~owed that a total amount of about 80 ng of bovine serum albumin (BSA), dispersed in fo,:r depots, resulted in serum antibodies, provided that the antigen was immobilized on activated Sepharose beads 2. It was clearly easier to obtain an antibody response using minute amounts of immunogen by the intrasplenic route

"Department of Human Anatomy, and 2Department of Medical and Physiological Chemistn/" Uppsala University. The Biomedical Centre, 5-751 23 UpDsala, Sweden.

10

amounts of antigen

B. Ove Nilsson I and Anders Larsson z

than by intraperitoneal or intravenous routes s,6. Spitz et aL 7 independently reported production of antibodies after a single intrasplenic injection of either 20 IJg of soluble antigen or of 2.5 x 105 allogeneic cells. These findings were extended in subsequent publications 8,9.

An antibody response was also obtained when the immunogen was immobilized on nitrocellulose paper, which then served as the carrier for immunization 2.s. This technique thus provides an easy way to immunize with electroblo~ed antigens after, for instance, electrophor- etic purification of proteins, and less than 1 p.g protein is sufficient for immunization by this method.

The success of intrasplenic immunization seems to be due to the deposition of the immunogen directly into the spleen, thus avoiding the losses associated with systemic injections, and to the immobilizing of the immunogen within the spleen, thus prolonging its exposition to the antigen-presenting cells. A requirement of the technique is that no toxic or irritating additive is used within the spleen since this would affect spleen cell function.

Immunogen carriers Any type of small, inert and non-toxic material that can

keep the immunogen in place while permitting its slow release is suitable. The immobilization of the immunogen on a matrix can be achieved nonspecifically or specifically:

(~ 1990. Elsevier Sc ence Pubhshers Ltd. UK 0167 4919/89/$02.00