Structural relatedness of distinct determinants recognized by monoclonal antibody TP25.99 on 132~microglobulin-associated and 32-5lmxoglobulin free HLA class I heavy chares

S. A. Demi, X. Wang, E. Y.J. Noroaha, Q. Zhou, V. Rebmaan, H. Grosse-Wilde, F. J. Moy, R. Powers, S. Ferrone

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)3275-3283
Number of pages9
JournalJournal of Immunology
Volume165
Issue number6
StatePublished - Sep 15 2000

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Demi, S. A., Wang, X., Noroaha, E. Y. J., Zhou, Q., Rebmaan, V., Grosse-Wilde, H., Moy, F. J., Powers, R., & Ferrone, S. (2000). Structural relatedness of distinct determinants recognized by monoclonal antibody TP25.99 on 132~microglobulin-associated and 32-5lmxoglobulin free HLA class I heavy chares. Journal of Immunology, 165(6), 3275-3283.