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We have cloned 26 different class I genes that are located in the major histocompatibility complex o f the C57BL/10 mouse. T w o o f the three class Γ genes found in the H-2 complex encode the H-2K b and H 2 D b antigens; the other 23 class I genes map to the adjacent T la complex. We have grouped the cosmids containing these genes into three clusters: one cluster links the H-2K and FA regions, one cluster links the H-2D and Qa-2 regions, and the final cluster maps to the T L region. The class I gene organizations in the Qa-2 and T L regions o f the C57BL/10 and BALB/c mice are generally similar, but there are several polymorphic segments. The Qa-2 region o f both mice seems to have evolved by the duplication o f gene pairs; furthermore , the H-2K region may have been generated by the translocation o f a gene pair f rom the Qa-2 region. We have evidence that several o f the genes in the Qa-2 region are expressed.— Devlin, J . J . ; Widera, G.; Mellor, A . L . ; Fahrner, Κ.; Sherman, D.; Weiss, Ε. H.; Flavell, R. A. Evolution and expression o f the transplantation antigen gene family. Federation Fror. 44: 2736-2740; 1985. I n 1937 G o r e r r e p o r t e d tha t cell surface ant igens m a p p i n g to what is now cal led the ma jo r h i s tocompat i ­ b i l i t y comp lex ( M H C ) were responsi­ ble f o r a l l ogra f t r e j ec t i on (6). I t has recent ly been shown tha t these class I M H C antigens are encoded by on ly a few members o f a large gene f ami l y (14, 16) (F ig . la). Class I antigens consist o f a ~ 4 5 , 0 0 0 d a l t o n glyco­ p r o t e i n a n d the separately encoded, noncova lent ly associated, 12,000-dal t o n ^ m i c r o g l o b u l i n ; these he t e rod i mers are usually expressed o n the cell surface, b u t some class I molecules may be secreted (9). W e have isolated 26 d i f f e rent class I heavy cha in genes f r o m C 5 7 B L / 1 0 (B IO) mouse (/; haplotype) ; we have mapped a l l o f these genes to the M H C , located o n chro ­ mosome 17 i n the mouse (Fig. lb). T w o o f the three class I genes tha t we have mapped to the H-2 complex , H-2Kb and H-2Db, encode the type o f h i s tocompat ib i l i t y ant igens r e p o r t e d by Gore r . These H-2 antigens have an essen­ t ia l ro le i n the detec t ion o f f o r e i gn ant igens o n the cell surface (3). Fo r example , v i ra l l y in fec ted cells are rec­ ognized a n d lysed by cy to tox i c Τ lymphocytes ( C T L ) on ly when v i r a l g lycoprote ins on the surface o f the in fec ted cel l are recognized i n asso­ c ia t ion w i t h class I H-2 antigens. T h e r e cogn i t i on o f f o re ign ant igens on a w ide var ie ty o f cell types is made possible by the expression class I H-2 antigens on v i r tua l l y a l l nucleated cells. M o r e than 50 d i f f e rent alleles o f H-2K a n d H-2D have been i d e n t i ­ fied; this ex t rao rd inary po l ymorph i sm may be necessary to a l low the p o p u ­ la t i on t o recognize many d i f f e r en t f o r e i gn ant igens (7). T h e less po ly ­ m o r p h i c class I ant igens encoded i n the T l a complex (e.g., Q a 2 , T L ) are expressed on ly o n cer ta in l ymphocy t e popu la t i ons , a n d a l t h o u g h the ma jo r ­ i ty o f class I genes lie i n the T l a complex , the f u n c t i o n o f the i r gene produc ts is n o t k n o w n . T o d e t e rm ine the o rgan i za t i on o f this gene fami ly , we screened cosmid l ibrar ies by using class I c D N A clones (13) as probes a n d isolated over 100 cosmids, each c on ta in ing an insert o f ~ 4 0 kilobases (kb) o f m u r i n e D N A . By res t r i c t i on m a p p i n g a n d c h r o m o ­ somal w a l k i n g exper iments , we have a r ranged these clones i n t o j u s t t h r e e clusters o f o ve r l app ing cosmids. O n e cluster l inks the H-2K and I-A regions; one c luster l inks the H-2D and Qa-2 reg ions; a n d the f ina l c luster maps t o the TL r e g i on . T H E H-2K REGION T h e t w o class I genes Kl and Kb shown i n F ig . 2 were m a p p e d to the H-2K r e g i o n by r e s t r i c t i on f r agmen t l e n g t h p o l y m o r p h i s m s (16) ; a s imi lar gene p a i r has been m a p p e d t o the H2K r e g i o n o f the B A L B / c mouse (d hap lo type ) (14 ) . L cells t r a n s f o r m e d w i t h t h e Kb gene expressed the a n t i g e n as d e t e r m i n e d by b o t h C T L a n d a n t i g e n b i n d i n g assays (10). These class I genes have been l i n k e d t o t h e new l y i d en t i f i e d Aß3 class I I sequence, w h i c h we iso lated by using an Aßl p r o b e . Prev ious ly i den t i f i ed 1 From the Minisymposium Molecular Biology and Chemistry of MHCand Tla-Encoded Molecules presented at the 68th Annual Meet ing o f The American Association o f Immunologists, St. Louis, Missouri, June 4, 1984. Accepted for publication September 27, 1984. 2736 0014-9446/85/0044-2736/$01.25. © FASEB 5 6 7 8 UT • I 1 1 ^ — 3'