In jawed vertebrates the V-(D)-J rearrangement is the main mechanism generating limitless variations of antigen-specific receptors, immunoglobulins (IGs), and T-cell receptors (TCRs) from few genes. Once the initial diversity is established in primary lymphoid organs, further diversification occurs in IGs by somatic hypermutation, a mechanism from which rearranged TCR genes were thought to be excluded. Here, we report the locus organization and expression of the T-cell receptor gamma (TCRG) genes in the Arabian camel (Camelus dromedarius). Expression data provide evidence that dromedary utilizes only two TCRG V-J genomic arrangements and, as expected, CDR3 contributes the major variability in the V domain. The data also suggest that diversity might be generated by mutation in the productively rearranged TCRGV genes. As for IG genes, the mutational target is biased toward G and C bases and (A/G/T)G(C/T)(A/T) motif (or DGYW). The replacement and synonymous substitutions (R/S) ratios in TCRGV regions are higher for CDR than for framework region, thus suggesting selection toward amino acid changes in CDR. Using the counterpart human TCR γδ receptor as a template, structural models computed adopting a comparative procedure show that nonconservative mutations contribute to diversity in CDR2 and at the γδ V domain interface.

Generation of diversity by somatic mutation in the Camelus dromedarius T-cell receptor gamma variable domains / Vaccarelli G;Antonacci R;Tasco G;Yang F;Giordano L;El Ashmaoui HM;Hassanane MS;Massari S;Casadio R;Ciccarese S. - In: EUROPEAN JOURNAL OF IMMUNOLOGY. - ISSN 0014-2980. - STAMPA. - 42:12(2012), pp. 3416-3428. [10.1002/eji.201142176]

Generation of diversity by somatic mutation in the Camelus dromedarius T-cell receptor gamma variable domains.

TASCO, GIANLUCA;CASADIO, RITA;
2012

Abstract

In jawed vertebrates the V-(D)-J rearrangement is the main mechanism generating limitless variations of antigen-specific receptors, immunoglobulins (IGs), and T-cell receptors (TCRs) from few genes. Once the initial diversity is established in primary lymphoid organs, further diversification occurs in IGs by somatic hypermutation, a mechanism from which rearranged TCR genes were thought to be excluded. Here, we report the locus organization and expression of the T-cell receptor gamma (TCRG) genes in the Arabian camel (Camelus dromedarius). Expression data provide evidence that dromedary utilizes only two TCRG V-J genomic arrangements and, as expected, CDR3 contributes the major variability in the V domain. The data also suggest that diversity might be generated by mutation in the productively rearranged TCRGV genes. As for IG genes, the mutational target is biased toward G and C bases and (A/G/T)G(C/T)(A/T) motif (or DGYW). The replacement and synonymous substitutions (R/S) ratios in TCRGV regions are higher for CDR than for framework region, thus suggesting selection toward amino acid changes in CDR. Using the counterpart human TCR γδ receptor as a template, structural models computed adopting a comparative procedure show that nonconservative mutations contribute to diversity in CDR2 and at the γδ V domain interface.
2012
Generation of diversity by somatic mutation in the Camelus dromedarius T-cell receptor gamma variable domains / Vaccarelli G;Antonacci R;Tasco G;Yang F;Giordano L;El Ashmaoui HM;Hassanane MS;Massari S;Casadio R;Ciccarese S. - In: EUROPEAN JOURNAL OF IMMUNOLOGY. - ISSN 0014-2980. - STAMPA. - 42:12(2012), pp. 3416-3428. [10.1002/eji.201142176]
Vaccarelli G;Antonacci R;Tasco G;Yang F;Giordano L;El Ashmaoui HM;Hassanane MS;Massari S;Casadio R;Ciccarese S
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/144484
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