The association of HLA class ~ I heavy chains with ~2-microglobulin (~2m) changes their antigenic profile. As a result, Abs react with elther ~2m-free or l~2m-associated HLA class ! heavy chains. An exception to this rule is the mAb TP25.99, which reacts with both lt2m-associated and ~2m-free HLA class I heavy chains. The reactivity with ~2m-associated HLA class I heavy chains is mediated by a conformational determinant expressed on all HLA-A, -B, and -C Ags. Tills determinant has been mapped to amino acid residues 194-198 in the a~3 domain. The reactivity with ~2m-free HLA class I heavy chains is mediated by a linear determinant expressed on all HLA-B Ags except the ~LA-B73 allospecificity and on <50% of HLA-A allospecificities. The latter determinant has been mapped to amino acid residues 239-242, 245, and ?,,gig in the ~x3 domain. The conformational and the linear determinants share several structural features, but have no homology in their amino acid sequence, mAb TF25.99 represents the first example of a mAb recognizing two distinct and spatially distant determinants on a protein. The structural homology of a linear and a conformational determinant on an antigenic entity provides a molecular mechanism for the sharing of specificity by B and TCRs.
ASJC Scopus subject areas
- Immunology and Allergy