Abstract
HLA DQ8 (DQ A1*0301/DQB1*0302) molecule is implicated in the susceptibility to insulin dependent diabetes mellitus whereas, HLA DQ6 (DQA1*0103/DQB1*0601) molecule may have a protective effect. In this study we used mice transgenic to HLA DQ8 and HLA-DQ6 to elucidate the T cell determinants on a putative islet cell target antigen, insulin. These mice do not express endogenous mouse class II heterodimers on cell surface. Using overlapping synthetic peptides spanning the complete sequence of human pre- proinsulin, we identified the sequences recognized by T cells in DQ8 transgenic mice and compared these to those in DQ6 transgenic mice. We observed a differential pattern of recognition of epitopes on human pre- proinsulin (HPI) polypeptide presented by the HLA DQ8 allele as compared to HLA DQ6. The sequences 1-24 and 44-63 were immunodominant in DQ8 transgenic mice while DQ6 transgenic mice primarily recognized sequences 14-33 and 74- 93 of HPI. We found that the immune response generated in HLA DQ8 transgenic mice against HPI 1-24 cross-reacted to the mouse pre-proinsulin sequence 1- 24. The T cell response were specifically inhibited using anti-CD4 and anti- DQ8 monoclonal antibodies. This cross-recognition of self sequences raises the possibility of modulation of experimental diabetes using this peptide.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 21-29 |
| Number of pages | 9 |
| Journal | Human Immunology |
| Volume | 58 |
| Issue number | 1 |
| DOIs | |
| State | Published - Nov 1 1997 |
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ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
Cite this
T cell recognition of human pre-proinsulin peptides depends on the polymorphism at HLA DQ locus : A study using HLA DQ8 and DQ6 transgenic mice. / Raju, Raghavan Pillai; Munn, Stephen R.; David, Chella S.
In: Human Immunology, Vol. 58, No. 1, 01.11.1997, p. 21-29.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - T cell recognition of human pre-proinsulin peptides depends on the polymorphism at HLA DQ locus
T2 - A study using HLA DQ8 and DQ6 transgenic mice
AU - Raju, Raghavan Pillai
AU - Munn, Stephen R.
AU - David, Chella S.
PY - 1997/11/1
Y1 - 1997/11/1
N2 - HLA DQ8 (DQ A1*0301/DQB1*0302) molecule is implicated in the susceptibility to insulin dependent diabetes mellitus whereas, HLA DQ6 (DQA1*0103/DQB1*0601) molecule may have a protective effect. In this study we used mice transgenic to HLA DQ8 and HLA-DQ6 to elucidate the T cell determinants on a putative islet cell target antigen, insulin. These mice do not express endogenous mouse class II heterodimers on cell surface. Using overlapping synthetic peptides spanning the complete sequence of human pre- proinsulin, we identified the sequences recognized by T cells in DQ8 transgenic mice and compared these to those in DQ6 transgenic mice. We observed a differential pattern of recognition of epitopes on human pre- proinsulin (HPI) polypeptide presented by the HLA DQ8 allele as compared to HLA DQ6. The sequences 1-24 and 44-63 were immunodominant in DQ8 transgenic mice while DQ6 transgenic mice primarily recognized sequences 14-33 and 74- 93 of HPI. We found that the immune response generated in HLA DQ8 transgenic mice against HPI 1-24 cross-reacted to the mouse pre-proinsulin sequence 1- 24. The T cell response were specifically inhibited using anti-CD4 and anti- DQ8 monoclonal antibodies. This cross-recognition of self sequences raises the possibility of modulation of experimental diabetes using this peptide.
AB - HLA DQ8 (DQ A1*0301/DQB1*0302) molecule is implicated in the susceptibility to insulin dependent diabetes mellitus whereas, HLA DQ6 (DQA1*0103/DQB1*0601) molecule may have a protective effect. In this study we used mice transgenic to HLA DQ8 and HLA-DQ6 to elucidate the T cell determinants on a putative islet cell target antigen, insulin. These mice do not express endogenous mouse class II heterodimers on cell surface. Using overlapping synthetic peptides spanning the complete sequence of human pre- proinsulin, we identified the sequences recognized by T cells in DQ8 transgenic mice and compared these to those in DQ6 transgenic mice. We observed a differential pattern of recognition of epitopes on human pre- proinsulin (HPI) polypeptide presented by the HLA DQ8 allele as compared to HLA DQ6. The sequences 1-24 and 44-63 were immunodominant in DQ8 transgenic mice while DQ6 transgenic mice primarily recognized sequences 14-33 and 74- 93 of HPI. We found that the immune response generated in HLA DQ8 transgenic mice against HPI 1-24 cross-reacted to the mouse pre-proinsulin sequence 1- 24. The T cell response were specifically inhibited using anti-CD4 and anti- DQ8 monoclonal antibodies. This cross-recognition of self sequences raises the possibility of modulation of experimental diabetes using this peptide.
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UR - http://www.scopus.com/inward/citedby.url?scp=0031456751&partnerID=8YFLogxK
U2 - 10.1016/S0198-8859(97)00212-7
DO - 10.1016/S0198-8859(97)00212-7
M3 - Article
C2 - 9438206
AN - SCOPUS:0031456751
VL - 58
SP - 21
EP - 29
JO - Human Immunology
JF - Human Immunology
SN - 0198-8859
IS - 1
ER -