Analysis of variable region of T-cell receptor beta chain usage in the human anti-porcine xenoresponse.
BACKGROUND
The human xenoreactive T-cell receptor (TCR) repertoire is not well documented. The aim of this study was to analyze the TCR repertoire in human anti-porcine xenoresponses.


METHODS
Peripheral blood lymphocytes (PBLs) from healthy donors were used to generate human T-cell lines against two different haplotypes of inbred Yucatan miniature swine (y/y and z/z). The variable region of TCR beta-chain (Vbeta) gene usage was determined by fluorescence CDR3 spectrotyping.


RESULTS
TCR Vbeta usage of an established human antiporcine T-cell line analyzed at weeks 5, 7, and 9 showed a sequential increase in Vbeta 1, 2, 6.2, 11, and 19 as compared to unprimed peripheral blood lymphocytes, whereas the usage of other Vbetas decreased. The selection of limited Vbeta genes correlated with the sequential increase in the specific lysis of the T-cell line, suggesting a non-random clonal selection and expansion of T-cell clones that recognized porcine targets. Different Vbeta restriction was found using the same peripheral blood lymphocytes against a different haplotype of swine, indicating this selection of Vbeta gene was swine leukocyte antigen-dependent.


CONCLUSIONS
There is restricted TCR Vbeta usage in the human anti-porcine response, suggesting that a limited number of xenogeneic epitopes are recognized by human T cells. The selection of particular TCR Vbeta clonotypes depends on the swine leukocyte antigen background.
Chen
M
M
Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Xu
X C
XC
Wu
W S
WS
Mohanakumar
T
T
D000818:Animals; D015478:Antigens, Heterophile / Q000276:immunology*; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D004730:Endothelium, Vascular / Q000276:immunology; D006239:Haplotypes; D006801:Humans; D007135:Immunoglobulin Variable Region; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D013552:Swine; D013556:Swine, Miniature; D013601:T-Lymphocytes / Q000276:immunology; D014183:Transplantation, Heterologous
D015478:Antigens, Heterophile; D007135:Immunoglobulin Variable Region; D016693:Receptors, Antigen, T-Cell, alpha-beta