Induction of Broadly Cross-Reactive Cytotoxic T Cells Recognizing an HIV-1 Envelope Determinant

• Published in: Science (American Association for the Advancement of Science) Vol. 255; no. 5042; pp. 333 - 336
• Main Authors: Takahashi, Hidemi, Nakagawa, Yohko, Pendleton, Charles D., Houghten, Richard A., Yokomuro, Kozo, Germain, Ronald N., Berzofsky, Jay A.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 17.01.1992; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: Acquired immune deficiency syndrome; AIDS; AIDS Vaccines - immunology; AIDS/HIV; Amino Acid Sequence; Amino acids; Animals; Biological and medical sciences; Cell Line; Cell lines; Cell mediated cytotoxicity; Cross reaction; Cross Reactions; Epitopes - immunology; Fundamental and applied biological sciences. Psychology; Gene Products, env - genetics; Gene Products, env - immunology; HIV; HIV (Viruses); HIV 1; HIV Antigens - immunology; HIV Envelope Protein gp160; HIV-1 - immunology; human immunodeficiency virus; In Vitro Techniques; Medical research; Mice; Mice, Inbred BALB C; Microbiology; Molecular Sequence Data; Molecules; Protein Precursors - genetics; Protein Precursors - immunology; Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains; Sequence Homology, Nucleic Acid; Spleen cells; T cells; T lymphocytes; T-Lymphocytes, Cytotoxic - immunology; Vaccination; Vaccines; Viral envelopes; Virology; Viruses; Immunization; Antigenic determinant; Peptides; HIV-1 virus; Rodentia; Retroviridae; Cytotoxicity; Glycoproteins; Cellular immunity; Immunodominance; Virus; Vertebrata; Mammalia; Mouse; T-Lymphocyte; Cross reaction; Lentivirinae; Isolate; Property structure relationship; Human immunodeficiency virus; Virus envelope; Recognition
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1372448

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.