A mAb against HLA-A2 can be influenced both positively and negatively by the associated peptide.

Presentation of peptides by class I HLA molecules is essential for the development of a T cell-mediated immune response. TCRs have the ability to discriminate among large numbers of different HLA-peptide complexes. We have identified a mAb, MA2.1, that also discriminates among HLA-A2 associated with different peptides. A soluble form of HLA-A2 bound to single peptides was prepared and its serological reactivity was studied using four mAbs. Three antibodies, W6/32, BB7.2 and BBM.1, recognized all the complexes equally. MA2.1, however, recognized most of the complexes equally but showed markedly different reactivity to two peptides bound to HLA-A2. MA2.1 recognized HLA-A2 complexed with the HIV-1 p17 epitope (SLYNTVATL) at least 30 times more strongly than all other complexes studied and this enhanced reactivity was found to be sensitive to a point mutation of threonine to alanine at position 8 in the peptide. In addition, MA2.1 had a very low reactivity for HLA-A2 complexed with the peptide TLWVDPYEV. Previous studies have mapped the binding epitope of MA2.1 to the alpha 1 and alpha 2 helices of HLA-A2, suggesting two possible explanations for the ability of the bound peptide to influence MA2.1 reactivity. Either MA2.1 is sensitive to peptide-induced conformational changes of the helices, or it directly contacts certain peptides in the groove of HLA-A2.