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Science 17 January 1992:
Vol. 255. no. 5042, pp. 333 - 336
DOI: 10.1126/science.1372448
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Articles

Science, Vol 255, Issue 5042, 333-336
Copyright © 1992 by American Association for the Advancement of Science

articles

Induction of broadly cross-reactive cytotoxic T cells recognizing an HIV-1 envelope determinant

H Takahashi, Y Nakagawa, CD Pendleton, RA Houghten, K Yokomuro, RN Germain, and JA Berzofsky

Department of Microbiology and Immunology, Nippon Medical School, Tokyo, Japan.

An immunodominant determinant for cytotoxic T lymphocytes (CTLs) exists in the hypervariable portion of human immunodeficiency virus-1 (HIV-1) gp160. Three mouse CTL lines (specific for isolates MN, RF, and IIIB) were examined for recognition of homologous determinants from distinct isolates. Only MN-elicited CTLs showed extensive interisolate cross-reactivity. Residue 325 played a critical role in specificity, with MN-elicited CTLs responding to peptides with an aromatic or cyclic residue and IIIB-induced cells recognizing peptides with an aliphatic residue at this position. CTL populations with broad specificities were generated by restimulation of IIIB-gp160 primed cells with MN-type peptides that have an aliphatic substitution at 325. This represents an approach to synthetic vaccines that can generate broadly cross-reactive CTLs capable of effector function against a wide range of HIV isolates.


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