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The Journal of Immunology, 1999, 163: 301-311.
Copyright © 1999 by The American Association of Immunologists

Invariant or Highly Conserved TCR {alpha} Are Expressed on Double-Negative (CD3+CD4-CD8-) and CD8+ T Cells

Mei Han, Lisa Harrison, Patricia Kehn, Kimberly Stevenson, Jeffrey Currier and Mary Ann Robinson1

Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, Twinbrook II Facility, National Institutes of Health, Rockville, MD 20852

TCR {alpha} (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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