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1996-03-09
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Document 0138
DOCN M9650138
TI The T cell receptor gene usage by simian immunodeficiency virus
gag-specific cytotoxic T lymphocytes in rhesus monkeys.
DT 9605
AU Chen ZW; Shen L; Regan JD; Kou Z; Ghim SH; Letvin NL; Harvard Medical
School, Beth Israel Hospital, Boston, MA 02215,; USA.
Zchen@Bih.Harvard.edu
SO J Immunol. 1996 Feb 15;156(4):1469-75. Unique Identifier : AIDSLINE
MED/96164575
AB MHC class I-restricted CTL play an important role in limiting the spread
of HIV-1 in the infected individual. Elucidating the molecular
interactions of CTL with the virus is, therefore, of central importance
for characterizing the immune control of this infection. In exploring
this CTL response, we have defined the TCR usage by SIVmac Gag-specific
CTL in rhesus monkeys. Thirty-nine CTL clones were generated from PBL of
three SIVmac-infected monkeys expressing the MHC class I Mamu-A*01 gene
product, all of which were shown to recognize a single SIVmac Gag
peptide in association with Mamu-A*01. Sixty-six percent of CTL clones
derived from two monkeys early after infection expressed TCR genes of
the V beta 13 family; 70% of these V beta 13+ CTL clones expressed a TCR
heterodimer composed of V alpha 1 and V beta 13 gene products. In
addition, there appeared to be a selection of a single conserved amino
acid and restricted CDR3 lengths in junctional regions of TCR
beta-chains expressed by the V beta 13+ CTL clones. These findings
indicate significant structural constraints on the CTL-TCR interaction
with the AIDS virus. Interestingly, 55% of the CTL clones derived from
the third animal at a later time following infection employed genes of
the V beta 6 family in their TCR. Despite the preferential use of TCR V
family genes by the CTL clones, the SIVmac Gag-specific CTL response was
clearly polyclonal; TCR expressed by these CTL clones displayed varied
sequences in their CDR3 regions. Other V gene families, including V beta
23, V alpha 8, and V alpha 20, were used in TCR expressed by SIVmac
Gag-specific CTL clones. These studies, therefore, indicate that the TCR
repertoire of SIVmac Gag-specific CTL that share a peptide and MHC class
I recognition specificity can be diverse. Such a broad CTL-TCR
repertoire may be advantageous for the host in containing an AIDS virus
infection.
DE Amino Acid Sequence Animal Antigens, Viral/CHEMISTRY/IMMUNOLOGY Base
Sequence Clone Cells Comparative Study Epitopes Gene Products,
gag/IMMUNOLOGY Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor
Gene Rearrangement, beta-Chain T-Cell Antigen Receptor Macaca mulatta
Molecular Sequence Data Peptides/IMMUNOLOGY Receptors, Antigen,
T-Cell, alpha-beta/*GENETICS Sequence Alignment Sequence Homology,
Amino Acid Support, U.S. Gov't, P.H.S. SIV/*IMMUNOLOGY T-Lymphocytes,
Cytotoxic/*IMMUNOLOGY JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).