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HLA DR3 mutations affecting antigen presentation
Abstracts
123
However, the possibility of transmitting imecdous agents such as HIV has complicated the use of blood products for immunotherapy. Recent immunologic studies done in our laboratory have identiffed TLX antigens in seminal plasma, and we have immunocymtoxicaily identified the ceils in seminal vesicles that contribute TLX antigens to seminal plasma. In light of these findings, we have designed and are carrying out a double blind, placebo contrulled clinical ~ wherein tint-degree aborting women are treated with vaginal suppositories that contain pooled seminal plasmas as the source of TLX stimulation. Some results from this trial and further characterization of seminal plasma TLX antigens are presented.
(118) H L A D R 3 M u t a t i o n s A f f e c t i n g A n t i g e n P r e s e n t a t i o n E. Mellins, B. Arp, and D. Pious
Department of Pedia:rics, U niversily of Washington, Sea:de, WA We are interested in the molecular interacdom and intracellular pathways involved in HLA-restr/cted presentation of soluble antigen to T cells. Using immunoselection, we have isolated eight independent DR3~I mutant B-LCLs with a variety of defects in antigen presentation. Several have a selective loss in antigen-presenting capacity, as demonstrated by their inability to stimulate some but not ttl of a panel of DR3-restricted T ceils specific for different solui~'a antigens. One mutant is unable to stimulate any DR3-resttqcted T cells tested but stimulates DP restricted T ceils normally. DIqA sequen.cing o f the mutant DR genes reveals that s~agle amino acid substitut/om in different regions of the D I ~ I domain underlie these different functional phenotypes. A second group ofimmutmselected mutants are unable to present whole protein antigen but present immuaogeaic pel~tlde effectively. The DR3 molecules in these mutants are altered in the expression of several polymo~hlc determinants tested, and yet the mutations appear to lie outside the DR structural genes. These mutants appear to have defects in the processing of solubte proteins to imraunogenic peptides.
(119) Lack o f I n t e r a c t i o n o f G M A l l o t y p e s w i t h H I , i n I D D M L M . Meske, M. Embling, M. Berkaw, J.IL Rowe, J.P. Pandey, and M.J. Sheehy
Red Cross Blood Semices, Madison, WI, Medical Universi:y of Sou:b Catalina, Charlatou, SC Because of conflicting previous reports showing the presence or absence of Gm-FILA interaction in IDDM, we report results for a group of Wisconsin multiplex families. Like others, we found no direct correlation between GM and IDDM. Our dam were very similar to those of Field et eL (AmJ Hum Genet 39:640), who interpreted their family study dam m indicate HLA-Gm interaction. GM Phenotype Conc_or~ar.,elDiscordance Field et al. Data
Wisconsin data
HLA IBD
Concordant
Discordant
2 1 0
9 4 0
3 9 1
Total
13 ( E x p = 11)
13 ( E x p = 15)
Concordant
Wisconsin expected
Discordant
Concordant
Discordant
9 4 2
2 6 1
8.04 5.07 1.61
2.96 4.93 1.39
15
9
14.71
9.29
Like Field et al., we found an excess of Gm phenotypic identity in sib pairs sharing two HLA haplotypes (9/11 pairs concordant) compared with those sharing one or zero haplotypes (6/13 pairs concordant, p = 0.084). However, because different Gm phenorypes can give the same phenotype, one must calculate the expected number of Gin-concordant pairs in each HLA IBD category. When both parents have the Gm pheuotTpe 3;23;5, any pair of childten is almost certain to have the same phenotype. In o ~
123
However, the possibility of transmitting imecdous agents such as HIV has complicated the use of blood products for immunotherapy. Recent immunologic studies done in our laboratory have identiffed TLX antigens in seminal plasma, and we have immunocymtoxicaily identified the ceils in seminal vesicles that contribute TLX antigens to seminal plasma. In light of these findings, we have designed and are carrying out a double blind, placebo contrulled clinical ~ wherein tint-degree aborting women are treated with vaginal suppositories that contain pooled seminal plasmas as the source of TLX stimulation. Some results from this trial and further characterization of seminal plasma TLX antigens are presented.
(118) H L A D R 3 M u t a t i o n s A f f e c t i n g A n t i g e n P r e s e n t a t i o n E. Mellins, B. Arp, and D. Pious
Department of Pedia:rics, U niversily of Washington, Sea:de, WA We are interested in the molecular interacdom and intracellular pathways involved in HLA-restr/cted presentation of soluble antigen to T cells. Using immunoselection, we have isolated eight independent DR3~I mutant B-LCLs with a variety of defects in antigen presentation. Several have a selective loss in antigen-presenting capacity, as demonstrated by their inability to stimulate some but not ttl of a panel of DR3-restricted T ceils specific for different solui~'a antigens. One mutant is unable to stimulate any DR3-resttqcted T cells tested but stimulates DP restricted T ceils normally. DIqA sequen.cing o f the mutant DR genes reveals that s~agle amino acid substitut/om in different regions of the D I ~ I domain underlie these different functional phenotypes. A second group ofimmutmselected mutants are unable to present whole protein antigen but present immuaogeaic pel~tlde effectively. The DR3 molecules in these mutants are altered in the expression of several polymo~hlc determinants tested, and yet the mutations appear to lie outside the DR structural genes. These mutants appear to have defects in the processing of solubte proteins to imraunogenic peptides.
(119) Lack o f I n t e r a c t i o n o f G M A l l o t y p e s w i t h H I , i n I D D M L M . Meske, M. Embling, M. Berkaw, J.IL Rowe, J.P. Pandey, and M.J. Sheehy
Red Cross Blood Semices, Madison, WI, Medical Universi:y of Sou:b Catalina, Charlatou, SC Because of conflicting previous reports showing the presence or absence of Gm-FILA interaction in IDDM, we report results for a group of Wisconsin multiplex families. Like others, we found no direct correlation between GM and IDDM. Our dam were very similar to those of Field et eL (AmJ Hum Genet 39:640), who interpreted their family study dam m indicate HLA-Gm interaction. GM Phenotype Conc_or~ar.,elDiscordance Field et al. Data
Wisconsin data
HLA IBD
Concordant
Discordant
2 1 0
9 4 0
3 9 1
Total
13 ( E x p = 11)
13 ( E x p = 15)
Concordant
Wisconsin expected
Discordant
Concordant
Discordant
9 4 2
2 6 1
8.04 5.07 1.61
2.96 4.93 1.39
15
9
14.71
9.29
Like Field et al., we found an excess of Gm phenotypic identity in sib pairs sharing two HLA haplotypes (9/11 pairs concordant) compared with those sharing one or zero haplotypes (6/13 pairs concordant, p = 0.084). However, because different Gm phenorypes can give the same phenotype, one must calculate the expected number of Gin-concordant pairs in each HLA IBD category. When both parents have the Gm pheuotTpe 3;23;5, any pair of childten is almost certain to have the same phenotype. In o ~