HIV ENVELOPE PROTEIN IS RECOGNIZED AS AN ALLOANTIGEN BY HUMAN DR-SPECIFIC ALLOREACTIVE T-CELLS

Recent studies from this laboratory reported the mapping of the full profile of T-cell allorecognition regions of HLA-DR2-beta subunit. The results indicated the presence of an allodeterminant within DR2-beta regions 141-156. In another study, we have shown that this allodeterminant is one of five regions of structural homology between the DR2-beta molecule and the HIV-envelope protein gp120 region 254-268. The fact that gp120 peptide 254-268 is homologous to the allodeterminant within the DR2-beta region 141-156 prompted us to investigate whether synthetic gp120 peptide 254-272 is recognized by human DR2-specific alloreactive T-cell lines. Five human alloreactive T-cell lines were prepared that were specific for the DR2 molecule and did not recognize DR1. These lines mounted in vitro proliferative responses to the allodeterminant peptide DR141-156 and also responded to the DR-similar peptide gp254-272. Removal of the residues 262-272 from the gp120 peptide (i.e., peptide 254-263) resulted in essentially complete loss of its proliferative activity. The effect of deletion of three residues of homology (Val-Val-Ser) at the N terminal (i.e., peptides DR145-156 and gp257-272) was examined. Peptide DR2-beta-145-156 exhibited very low stimulating activity, whereas peptide gp257-272 did not cause T-cell proliferative responses in any of the alloreactive T-cell lines. The T-cell lines did not respond to unrelated peptide controls, thus further confirming the specificity of these responses. These findings indicate that the virus is recognized as an alloantigen by human alloreactive DR2-specific T cells.