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Heterogeneity of DRw13 and DRw14 haplotypes in three populations
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#148 10.1
Abstracts HETEROGENEITY OF DRwI3 AND DRwI4 HAPLOTYPES IN THREE POPULATIONS. M A F e r n a n d e z - V i n a , ME Moraes, X Gao and P Stastny, D e p a r t m e n t of I n t e r n a l M e d i c i n e , U n i v e r s i t y of T e x a s S o u t h w e s t e r n M e d i c a l Center, Dallas, TX. We h a v e a n a l y z e d b y P C R and o l i g o n u c l e o t i d e h y b r i d i z a t i o n the DRBI, DRB3, DQAI, and DQBI a l l e l e s a s s o c i a t e d w i t h DRw6. I n c l u d e d in t h i s s t u d y w e r e 194 N A m e r i c a n C a u c a s o i d s , 64 Blacks (35 N. A m e r i c a n and 29 Brazilian) a n d 58 Latin A m e r i c a n u n r e l a t e d normal i n d i v i d u a l s . We a l s o s t u d i e d 20 i n f o r m a t i v e f a m i l i e s and 85 w o r k s h o p B cell lines. We found ii h a p l o t y p e s a s s o c i a t e d w i t h DRwI3 a n d 4 h a p l o t y p e s with DRwI4. T h e y i n c l u d e d t h r e e v a r i a n t s w h i c h h a d not b e e n p r e v i o u s l y r e c o g n i z e d h e r e c a l l e d D R B I * I 3 . 4 , DRBI*I4.3, and DQBI*6.5. T h e DRwI3 h a p l o t y p e s : Dw 18 18 19 19v HAG DRB3 0101 0202 0301 0301 0301 0301 0301 0101 0101 0202 0202 DRBI 1301 1301 1301 1302 1302 1302 1302 1303 1303 1303 13.4 DQAI 0103 0103 0103 0102 0102 0102 0102 0501 0201 0201 0201 DQBI 0603 0603 0603 0604 6.5 0501 0502 0301 0201 0201 0201 CAU 9 4 0 13 4 2 0 2 0 0 0 LAT 3 1 1 1 0 1 1 2 0 0 1 BLK 3 2 1 2 1 3 0 1 1 1 1 D R B I * I 4 0 1 o c c u r r e d in two l i n k a g e groups, w i t h D R B 3 * 0 2 0 1 and DRB3*0202. D R B I * I 4 0 2 (Dwl6) w a s seen o n l y in L a t i n Am. donors and was associated with DQAI*0501,DQBI*0301. D R B I * I 4 . 3 d i f f e r e d from 1402 in c o d o n 86. O u r r e s u l t s show an i m p r e s s i v e h e t e r o g e n e i t y of DRw6 h a p l o t y p e s t h a t can now be e a s i l y i d e n t i f i e d by DNA typing.
BIOLOGICAL RELEVANCE OF EVOLUTIONARY CONSERVED TRANS-SPECIES MHC POLYMORPHISMS. RE Bontroo. BG Elferink, N Otting, M Jonker and RRP de Vries, ITRI-TNO, Primate Center, Lange Kleiweg 151, Rijswijk, The Netherlands. Sequence studies demonstrated that the origin of a considerable proportion of MHC allelic variety predates the divergence of man and non-human primates. However, various related trans-species MHC alleles originating from one ancestral allele, as present in distinct primate species, display a certain degree of sequence variation. In this context, it is of interest to study whether structural similarities in trans-species MHC alleles can be translated into functional data. Antigen presentation studies demonstrated that chimpanzee antigen presenting cells can present antigen (PPD) to human T helper cells (and vice versa). The HLA- and Patr-DRw52 molecules reactive with monoclonal antibody 7.3.19.1 were shown to function as restriction elements when antigen (PPD) was presented across this particular species barrier. It is concluded that the restriction determinants essential for the presentation of Mycobacterium tuberculosis antigens may have been conserved in evolution due to a selective advantage. It is also noted that some amino-acid substitutions in trans-species MHC alleles are apparently not influencing the successful presentation of PPD. For that reason, these kind of studies may allow us to pinpoint which part of evolutionary conserved MHC polymorphisms are critical for biological functions such as antigen-binding and T-cell receptor recognition.
#147 10.1
#148 10.1
Abstracts HETEROGENEITY OF DRwI3 AND DRwI4 HAPLOTYPES IN THREE POPULATIONS. M A F e r n a n d e z - V i n a , ME Moraes, X Gao and P Stastny, D e p a r t m e n t of I n t e r n a l M e d i c i n e , U n i v e r s i t y of T e x a s S o u t h w e s t e r n M e d i c a l Center, Dallas, TX. We h a v e a n a l y z e d b y P C R and o l i g o n u c l e o t i d e h y b r i d i z a t i o n the DRBI, DRB3, DQAI, and DQBI a l l e l e s a s s o c i a t e d w i t h DRw6. I n c l u d e d in t h i s s t u d y w e r e 194 N A m e r i c a n C a u c a s o i d s , 64 Blacks (35 N. A m e r i c a n and 29 Brazilian) a n d 58 Latin A m e r i c a n u n r e l a t e d normal i n d i v i d u a l s . We a l s o s t u d i e d 20 i n f o r m a t i v e f a m i l i e s and 85 w o r k s h o p B cell lines. We found ii h a p l o t y p e s a s s o c i a t e d w i t h DRwI3 a n d 4 h a p l o t y p e s with DRwI4. T h e y i n c l u d e d t h r e e v a r i a n t s w h i c h h a d not b e e n p r e v i o u s l y r e c o g n i z e d h e r e c a l l e d D R B I * I 3 . 4 , DRBI*I4.3, and DQBI*6.5. T h e DRwI3 h a p l o t y p e s : Dw 18 18 19 19v HAG DRB3 0101 0202 0301 0301 0301 0301 0301 0101 0101 0202 0202 DRBI 1301 1301 1301 1302 1302 1302 1302 1303 1303 1303 13.4 DQAI 0103 0103 0103 0102 0102 0102 0102 0501 0201 0201 0201 DQBI 0603 0603 0603 0604 6.5 0501 0502 0301 0201 0201 0201 CAU 9 4 0 13 4 2 0 2 0 0 0 LAT 3 1 1 1 0 1 1 2 0 0 1 BLK 3 2 1 2 1 3 0 1 1 1 1 D R B I * I 4 0 1 o c c u r r e d in two l i n k a g e groups, w i t h D R B 3 * 0 2 0 1 and DRB3*0202. D R B I * I 4 0 2 (Dwl6) w a s seen o n l y in L a t i n Am. donors and was associated with DQAI*0501,DQBI*0301. D R B I * I 4 . 3 d i f f e r e d from 1402 in c o d o n 86. O u r r e s u l t s show an i m p r e s s i v e h e t e r o g e n e i t y of DRw6 h a p l o t y p e s t h a t can now be e a s i l y i d e n t i f i e d by DNA typing.
BIOLOGICAL RELEVANCE OF EVOLUTIONARY CONSERVED TRANS-SPECIES MHC POLYMORPHISMS. RE Bontroo. BG Elferink, N Otting, M Jonker and RRP de Vries, ITRI-TNO, Primate Center, Lange Kleiweg 151, Rijswijk, The Netherlands. Sequence studies demonstrated that the origin of a considerable proportion of MHC allelic variety predates the divergence of man and non-human primates. However, various related trans-species MHC alleles originating from one ancestral allele, as present in distinct primate species, display a certain degree of sequence variation. In this context, it is of interest to study whether structural similarities in trans-species MHC alleles can be translated into functional data. Antigen presentation studies demonstrated that chimpanzee antigen presenting cells can present antigen (PPD) to human T helper cells (and vice versa). The HLA- and Patr-DRw52 molecules reactive with monoclonal antibody 7.3.19.1 were shown to function as restriction elements when antigen (PPD) was presented across this particular species barrier. It is concluded that the restriction determinants essential for the presentation of Mycobacterium tuberculosis antigens may have been conserved in evolution due to a selective advantage. It is also noted that some amino-acid substitutions in trans-species MHC alleles are apparently not influencing the successful presentation of PPD. For that reason, these kind of studies may allow us to pinpoint which part of evolutionary conserved MHC polymorphisms are critical for biological functions such as antigen-binding and T-cell receptor recognition.