Invariant or highly conserved TCR alpha are expressed on double-negative (CD3+CD4-CD8-) and CD8+ T cells.
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.
Han
M
M
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, Rockville, MD 20852, USA.
Harrison
L
L
Kehn
P
P
Stevenson
K
K
Currier
J
J
Robinson
M A
MA
D000328:Adult; D000595:Amino Acid Sequence; D017252:CD3 Complex / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D015704:CD4 Antigens / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D019002:CD56 Antigen / Q000097:blood / Q000235:genetics; D016827:CD8 Antigens / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D017124:Conserved Sequence / Q000276:immunology*; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000378:metabolism; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000378:metabolism*; D014158:Transcription, Genetic / Q000276:immunology
D017252:CD3 Complex; D015704:CD4 Antigens; D019002:CD56 Antigen; D016827:CD8 Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta