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Are Expressed on Double-Negative (CD3+CD4-CD8-) and CD8+ T Cells
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, Twinbrook II Facility, National Institutes of Health, Rockville, MD 20852
TCR
(TCRA) expression was examined in RNA samples from PBMC and
isolated populations of CD4+, CD8+, and DN T
cells from 15 healthy individuals. The expressed TCR repertoire was
surveyed using spectratype analysis, a technique that displays the
distribution of complementarity determining region 3 (CDR3) lengths for
each TCRAV gene family. The results revealed the presence of unusual
populations of double-negative (DN;
CD4-CD8-CD3+) T cells that
express invariant or conserved TCRAV4A, AV7, AV19, and AV24 chains.
Each of the conserved TCRA families was over-represented in >70% of
the individuals studied, and all individuals expressed at least one of
the over-represented TCRAV families. Over-represented conserved AV4A or
AV7 sequences were also present in CD8+ T cells from most
donors. The extent of TCRA sequence conservation is unparalleled.
TCRAV4A, AV19, and AV24 sequences were invariant, although AV4A
and AV19 transcripts contained N region additions. TCRAV24 transcripts
derived from the direct juxtaposition of V and J gene segments. TCRAV7
sequences showed some diversity in two amino acids encoded at junctions
of V and J gene segments. Although derivation of DN T cells with
conserved TCRA chains is puzzling, the wide-spread expression of these
unusual cells suggests an important
function.
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