A single amino acid interchange yields reciprocal CTL specificities for HIV-1 gp160.
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.
Takahashi
H
H
Metabolism Branch, National Cancer Institute, Bethesda, MD 20892.
Merli
S
S
Putney
S D
SD
Houghten
R
R
Moss
B
B
Germain
R N
RN
Berzofsky
J A
JA
D000595:Amino Acid Sequence; D000818:Animals; D005805:Genes, MHC Class I; D019302:HIV Envelope Protein gp160; D015497:HIV-1 / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D012191:Retroviridae Proteins / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology*
D019302:HIV Envelope Protein gp160; D012191:Retroviridae Proteins; D014759:Viral Envelope Proteins