Contribution of T-cell receptor-contacting and peptide-binding residues of the class II molecule HLA-DR4 Dw10 to serologic and antigen-specific T-cell recognition.

摘要: Abstract The relative contributions of putative T-cell receptor (TCR)-contacting and peptide-binding residues a major histocompatibility complex (MHC) class II restriction element to serologic antigen-specific recognition were investigated by site-specific mutagenesis. Amino acids 70 71 in the DRβ1 domain cf DR4 Dw 10 are uniquely different from other subtypes DR4. Residues is predicted be located at membrane-distal surface molecule, where it may influence direct interaction with TCR. Residue form part antigen-binding groove its on mediated indirectly via an effect peptide binding. Trsnfected murine L cells produced expressing products Dw10B genes which codons for had been mutated towards Dw14. Support orientations β-chain was lent observation that only plays important role formation determinant. Mutation this residue sufficient produce recovery human monoclonal antibody, NI, has specificity all exception Dw10. clone HA1.7, specific influenza virus hemagglutinin (HA) 307–319 restricted DR1 Dw1, exhibits degeneracy MHC Dr4 DW10. Alteration Dw10 or alone failed rescue antigen HA1.7; both amino acid substitutions served as effective antigen-presenting cells, implying key recognition. doubly substituted more efficient HA1.7 than Dw14 Dw1. This implies conservative change leucine (DR1 Dw1 except Dw10) isoleucine (DR4 leads equivalent hetoroclitic response.