SPECIFIC LYSIS OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1-INFECTED CELLS BY A HLA-A3.1-RESTRICTED CD8+ CYTOTOXIC LYMPHOCYTE-T CLONE THAT RECOGNIZES A CONSERVED PEPTIDE SEQUENCE WITHIN THE GP41 SUBUNIT OF THE ENVELOPE PROTEIN

被引:50
作者
TAKAHASHI, K
DAI, LC
FUERST, TR
BIDDISON, WE
EARL, PL
MOSS, B
ENNIS, FA
机构
[1] UNIV MASSACHUSETTS,MED CTR,DEPT MED,DIV INFECT DIS,WORCESTER,MA 01655
[2] NINCDS,NEUROIMMUNOL BRANCH,BETHESDA,MD 20892
[3] NIAID,VIRAL DIS LAB,BETHESDA,MD 20892
关键词
AIDS; T-CELL EPITOPE;
D O I
10.1073/pnas.88.22.10277
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
A HLA-A3.1-restricted CD8+ cytotoxic T-cell clone, E7.20, that lyses cells infected with human immunodeficiency virus type 1 was isolated from an infected individual. The epitope was localized to amino acids 768-778 (RLRDLLLIVTR, NL43 env sequence) of the cytoplasmic domain of gp41 by successive use of a panel of recombinant vaccinia viruses that express truncated env genes and synthetic peptides. The epitope is conserved on 7 (NL43, BRU, HXB2, BRVA, SC, JH3, and JFL) of 13 human immunodeficiency virus type 1 isolates from North America. Synthetic peptides of this region of strains RF and CDC4 are also recognized by E7.20 despite a nonconservative Thr --> Val or Thr --> Ala change at amino acid 777; however, an MN peptide, which has four amino acid substitutions, was not reactive. The epitope recognized by E7.20 has a predicted hydrophobic alpha-helical structure, with three contiguous Leu residues followed by Ile and Val at amino acids 772-776. Cytotoxicity was restricted by HLA-A3.1 using allogeneic target cells that shared HLA class I antigens with the donor and an HLA-A and -B negative human plasma cell line transfected with the HLA-A3.1 gene. The transfected cells were infectable by human immunodeficiency virus type 1 strains IIIB and MN but only the former virus sensitized them to killing by E7.20. The ability of E7.20 to specifically lyse a human lymphocyte line infected with a human immunodeficiency virus type 1 strain carrying the conserved epitope is consistent with an important role for cytotoxic T cells in controlling infection.
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页码:10277 / 10281
页数:5
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