Nearly identical T-cell receptor V-gene usage at birth in two cohorts of distinctly different ethnic origin: influence of environment in the final maturation in the adult.
We have previously analysed the T-cell receptor (TCR) V-gene usage in peripheral blood T lymphocytes from a group of healthy Scandinavians, and described a biased representation (i.e. a statistically significant higher median representation) for some of the TCR V genes towards the CD4+ subpopulation. In a subsequent study the usage of the same V genes was analysed in single positive (CD4+ CD8- and CD4- CD8+) human thymocytes, and a similar type of skewness was noted. These observations might be explained by an influence of the specificity of the TCR of thymocytes on the maturation into the CD4+ or the CD8+ lineage. Such a model would assume an interaction between a common determinant on the major histocompatibility complex (MHC) class I or class II molecules, or with a peptide that is preferentially presented by either of the two molecules, and the TCR on the maturing thymocyte. To investigate the possible influence of a different genetic background and environment on skewed TCR V-gene representation, we have in this study analysed the TCR V-gene usage in peripheral blood and umbilical cord blood lymphocytes obtained from Asians, with a different ethnic and environmental background from our previous Scandinavian subjects. In the umbilical cord blood lymphocytes the TCR V-gene usage was close to identical between the two different ethnic groups in both CD4+ and CD8+ subpopulations. Analysing the peripheral blood lymphocyte (PBL) TCR V-gene usage, we found that three of the four monoclonal antibodies (MoAb) with a biased reactivity towards the CD4+ subpopulation in the Scandinavian group also showed a similar skewed reactivity in this study. Thus, the majority of the TCR V genes were used in a similar way. Some minor but definite discrepancies could be detected when comparing TCR V-gene usage in adult individuals from these two different ethnic groups. These differences could be inferred to be due to selective peripheral expansion through environmental pressure of T cells utilizing a specific V beta gene segment. We conclude that a striking preservation of biased TCR V-gene usage does exist in humans of distinctly different ethnic origin.
Department of Immunology, Karolinska Institute, Stockholm, Sweden.
N S
NS
Ramakrishnan
J
J
Grunewald
C H
CH
Janson
H
H
Wigzell
D000367:Age Factors; D000911:Antibodies, Monoclonal; D001208:Asia / Q000208:ethnology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005787:Gene Frequency; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D005796:Genes; D006801:Humans; D007231:Infant, Newborn; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D012537:Scandinavian and Nordic Countries / Q000208:ethnology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D000911:Antibodies, Monoclonal; D016693:Receptors, Antigen, T-Cell, alpha-beta