Induction of broadly cross-reactive cytotoxic T cells recognizing an HIV-1 envelope determinant.
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.
Department of Microbiology and Immunology, Nippon Medical School, Tokyo, Japan.
H
H
Takahashi
Y
Y
Nakagawa
C D
CD
Pendleton
R A
RA
Houghten
K
K
Yokomuro
R N
RN
Germain
J A
JA
Berzofsky
D016915:AIDS Vaccines / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D003429:Cross Reactions; D000939:Epitopes / Q000276:immunology; D015686:Gene Products, env / Q000235:genetics / Q000276:immunology*; D015488:HIV Antigens / Q000276:immunology; D019302:HIV Envelope Protein gp160; D015497:HIV-1 / Q000276:immunology*; D066298:In Vitro Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011498:Protein Precursors / Q000235:genetics / Q000276:immunology*; D012689:Sequence Homology, Nucleic Acid; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014611:Vaccination
D016915:AIDS Vaccines; D000939:Epitopes; D015686:Gene Products, env; D015488:HIV Antigens; D019302:HIV Envelope Protein gp160; D011498:Protein Precursors