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NLM AIDSLINE

The 45 pocket of HLA-A2.1 plays a role in presentation of influenza virus matrix peptide and alloantigens.




 

J Immunol. 1991 May 15;146(10):3508-12. Unique Identifier : AIDSLINE

Amino acid substitutions were introduced into the 45 pocket of HLA-A2.1 to determine the potential role of this structurally defined feature of class I molecules in viral peptide and alloantigen presentation. The 45 pocket lies below the alpha 1-domain alpha-helix and is composed of five amino acids, three of which differ between HLA-A2.1 and HLA-B37. These two class I molecules have previously been shown to have largely non-overlapping peptide-binding specificities. Site-directed mutagenesis was used to replace the hydrophobic residues at positions 24, 45, and 67 in the 45 pocket of HLA-A2.1 with the hydrophilic amino acids found in these positions in HLA-B37. Thus, three single amino acid mutants were produced: 24A----S, 45 M----T, and 67V----S. These mutants were transfected into HMy2.C1R cells and assessed for their ability to present influenza virus matrix M1 57-68 peptide and HTLV-I Tax-1 2-25 peptide to HLA-A2.1-restricted, peptide-specific CTL and to present alloantigens to HLA-A2-allospecific CTL lines. Each of these substitutions in the 45 pocket produced a molecule that failed to present the M1 peptide to most M1 peptide-specific CTL lines. In contrast, none of these mutations affected presentation of the Tax-1 peptide to Tax-1-specific CTL lines, which indicates that these mutant HLA-A2 molecules can function in viral peptide presentation. Two of the three substitutions in the 45 pocket resulted in lack of recognition by a subset of HLA-A2 allospecific CTL lines. These results demonstrate that the amino acid side chains in the 45 pocket can strongly influence peptide presentation and suggest that the 45 pocket may play a role in determining peptide-binding specificity.

Base Sequence Gene Products, tax/IMMUNOLOGY Human HLA-A Antigens/GENETICS/*PHYSIOLOGY Isoantigens/*IMMUNOLOGY Models, Molecular Molecular Sequence Data Mutation Orthomyxoviruses Type A/*IMMUNOLOGY Structure-Activity Relationship T-Lymphocytes, Cytotoxic/IMMUNOLOGY Transfection Viral Matrix Proteins/*IMMUNOLOGY JOURNAL ARTICLE



 




Information in this article was accurate in August 30, 1991. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.