Inherent reactivity of unselected TCR repertoires to peptide-MHC molecules.
Proc Natl Acad Sci U S A
; 116(44): 22252-22261, 2019 10 29.
Article
em En
| MEDLINE
| ID: mdl-31570608
ABSTRACT
The repertoire of αß T cell antigen receptors (TCRs) on mature T cells is selected in the thymus where it is rendered both self-tolerant and restricted to the recognition of major histocompatibility complex molecules presenting peptide antigens (pMHC). It remains unclear whether germline TCR sequences exhibit an inherent bias to interact with pMHC prior to selection. Here, we isolated TCR libraries from unselected thymocytes and upon reexpression of these random TCR repertoires in recipient T cell hybridomas, interrogated their reactivities to antigen-presenting cell lines. While these random TCR combinations could potentially have reacted with any surface molecule on the cell lines, the hybridomas were stimulated most frequently by pMHC ligands. The nature and CDR3 loop composition of the TCRß chain played a dominant role in determining pMHC-reactivity. Replacing the germline regions of mouse TCRß chains with those of other jawed vertebrates preserved reactivity to mouse pMHC. Finally, introducing the CD4 coreceptor into the hybridomas increased the proportion of cells that could respond to pMHC ligands. Thus, αß TCRs display an intrinsic and evolutionary conserved bias for pMHC molecules in the absence of any selective pressure, which is further strengthened in the presence of coreceptors.
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MEDLINE
Assunto principal:
Receptores de Antígenos de Linfócitos T alfa-beta
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Evolução Molecular
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Antígenos de Histocompatibilidade
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article