Allogeneic recognition of HLA-DRB1*0406 by T cells with HLA-DRB1*0403: role of amino acid residue 37 on the beta sheet in T cell recognition.

Five T cell clones reactive with allogeneic HLA-DR molecules were obtained by stimulating CD4+ T cells (DRB10403) with DRB10406-homozygous KT13 cells whose DR beta chain differed by a single amino acid residue (37) on the beta sheet from the DRB10403 product. Except for one T cell clone which had both auto- and alloreactivities, these clones proliferated by stimulation with KT13 but not with autologous cells, indicating that the single substitution at position 37 on the HLA-DR molecule was sufficient to alter the alloantigenicity of the DR molecule and to elicit an allogeneic T cell response. Two clones reacted with some but not all B cell lines with DRB10406, suggesting the possible involvement of a certain peptide whose distribution is restricted to some cells which form the alloantigenic structure recognized by these clones. The two remaining clones showed broad but distinct anti-DR specificity in addition to anti-DRB10406 reactivity, suggesting that they recognize the DRB10406-peptide complex whose antigenic structures also occur in some combinations of other DRB1 alleles with certain peptides bound to these alleles. The T cell clone with both auto- and alloreactivity was found to react with autologous monocytes but not with autologous B or T cells and to express lower TCR alpha beta than other T cell clones which showed no autoreactivity. The possible recognition molecule for this autoreactive T cell clone is discussed.