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Science 6 October 1989:
Vol. 246. no. 4926, pp. 118 - 121
DOI: 10.1126/science.2789433
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Articles

Science, Vol 246, Issue 4926, 118-121
Copyright © 1989 by American Association for the Advancement of Science

articles

A single amino acid interchange yields reciprocal CTL specificities for HIV-1 gp160

H Takahashi, S Merli, SD Putney, R Houghten, B Moss, RN Germain, and JA Berzofsky

Metabolism Branch, National Cancer Institute, Bethesda, MD 20892.

For the IIIB isolate of human immunodeficiency virus type-1 (HIV-1), the immunodominant determinant of the envelope protein gp160 for cytotoxic T lymphocytes (CTLs) of H-2d mice is in a region of high sequence variability among HIV-1 isolates. The general requirements for CTL recognition of peptide antigens and the relation of recognition requirements to the natural variation in sequence of the HIV were investigated. For this purpose, a CTL line specific for the homologous segment of the envelope from the MN isolate of HIV-1 and restricted by the same class I major histocompatibility (MHC) molecule (Dd) as the IIIB-specific CTLs was raised from mice immunized with MN-env-recombinant vaccinia virus. The IIIB-specific and MN-specific CTLs were completely non-cross-reactive. Reciprocal exchange of a single amino acid between the two peptide sequences, which differed in 6 of 15 residues, led to a complete reversal of the specificity of the peptides in sensitizing targets, such that the IIIB-specific CTLs lysed targets exposed to the singly substituted MN peptide and vice versa. These data indicate the importance of single residues in defining peptide epitopic specificity and have implications for both the effect of immune pressure on selection of viral mutants and the design of effective vaccines.


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