Tissue-specific peptides influence human T cell repertoire to porcine xenoantigens.
BACKGROUND
Human CD8+ T cells elicit a vigorous response to allo- or xenogeneic MHC class I molecules. However, the influence of a given MHC-bound peptide to the responding allo- or xenoreactive T cell repertoire is not clear.


METHODS
In this study, we analyzed individual T cell responses to unique tissue epitopes presented on syngeneic porcine endothelial and lymphoblastoid cells by limiting dilution analysis and analyzed the responding T cell repertoire by T cell receptor beta (TCR Vbeta) chain spectrotyping.


RESULTS
Both porcine endothelial and lymphoblastoid cells were able to elicit swine leukocyte antigen (SLA) class I restricted and peptide-dependent cytotoxic T lymphocyte (CTL) responses. The responding human CD8+ T cells showed a heterogenous but limited TCR Vbeta gene usage. Interestingly, although a large portion of the selected TCR Vbeta gene usage in response to endothelial and lymphoblastoid cells were shared (i.e., Vbeta-1, 2, 6.1, 13), unique Vbeta usage was noted in T cells that respond to either endothelial (Vbeta-5.3) or lymphoblastoid cells (Vbeta-5.1, 11), suggesting that porcine tissue-specific epitopes play a role in modulating the responding T cell repertoire. Limiting dilution cloning analysis revealed that a majority (89%) of the CTL clones stimulated by porcine endothelial cells recognized shared peptides presented by both endothelial cells and syngeneic lymphoblastoid cells. However, a significant portion (11%) of the CTL clones recognized unique peptides presented only in the context of SLA class I molecules on endothelial cells.


CONCLUSIONS
These results provide evidence for the first time that tissue-specific peptides can directly influence T cell repertoire in response to the xenogeneic stimulus.
Xu
X C
XC
Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Howard
T
T
Mohanakumar
T
T
D000818:Animals; D015478:Antigens, Heterophile / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology; D002460:Cell Line; D004727:Endothelium / Q000166:cytology / Q000276:immunology; D000939:Epitopes; D006801:Humans; D008214:Lymphocytes / Q000276:immunology; D010455:Peptides / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D013379:Substrate Specificity; D013552:Swine; D013556:Swine, Miniature; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D015478:Antigens, Heterophile; D001426:Bacterial Proteins; D000939:Epitopes; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta