Abstract
The CD8αα homodimer is crucial to both thymic T cell selection and the antigen recognition of cytotoxic T cells. The CD8-pMHC-I interaction can enhance CTL immunity via stabilizing the TCR-pMHC-I interaction and optimizing the cross-reactivity and Ag sensitivity of CD8+ T cells at various stages of development. To date, only human and mouse CD8-pMHC-I complexes have been determined. Here, we resolved the pBF2*1501 complex and the cCD8αα/pBF2*1501 and cCD8αα/pBF2*0401 complexes in nonmammals for the first time. Remarkably, cCD8αα/pBF2*1501 and the cCD8αα/pBF2*0401 complex both exhibited two binding modes, including an “antibody-like” mode similar to that of the known mammal CD8/pMHC-I complexes and a “face-to-face” mode that has been observed only in chickens to date. Compared to the “antibody-like” mode, the “face-to-face” binding mode changes the binding orientation of the cCD8αα homodimer to pMHC-I, which might facilitate abundant γδT cells to bind diverse peptides presented by limited BF2 alleles in chicken. Moreover, the forces involving in the interaction of cCD8αα/pBF2*1501 and the cCD8αα/pBF2*0401 are different in this two binding model, which might change the strength of the CD8-pMHC-I interaction, amplifying T cell cross-reactivity in chickens. The coreceptor CD8αα of TCR has evolved two peptide-MHC-I binding patterns in chickens, which might enhance the T cell response to major or emerging pathogens, including chicken-derived pathogens that are relevant to human health, such as high-pathogenicity influenza viruses.
Highlights
Critical molecules involved in immune defense can be subject to an evolving molecular arms race with all kinds of pathogens, of which the most famous has led to the multiple loci, high allelic polymorphism and high sequence diversity of major histocompatibility complex (MHC) genes (1)
The current study determined the structures of chicken CD8/pMHC-I complexes for the first time, namely, cCD8aa/pBF2*1501 and cCD8aa/ pBF2*0401, which each contain complex A and complex B in an asymmetrical unit. cCD8aa binds to pBF2*1501 and pBF2*0401 in an allele-dependent but peptide-independent manner, as demonstrated by the CD8aa-pMHC-I interaction in previous studies (38, 39)
CCD8aa binds to pBF2*1501 and pBF2*0401 in complex A of cCD8aa/pBF2*1501 and cCD8aa/ pBF2*0401 in a novel “face-to-face” mode, which is distinct from the antibody-like binding mode of the known human and mouse CD8/pMHC-I complexes (19, 35–37)
Summary
Critical molecules involved in immune defense can be subject to an evolving molecular arms race with all kinds of pathogens, of which the most famous has led to the multiple loci, high allelic polymorphism and high sequence diversity of major histocompatibility complex (MHC) genes (1). These genes encode the classical class I and class II (aka MHC-I/II) molecules that bind antigenic peptides and present them for recognition by the T cell receptor (TCR) on T lymphocytes bearing coreceptors CD8 and CD4, respectively (2). The multiple structural basis of T cell cross-reactivity has been explained, focusing on the interaction between TCR and pMHC-I and the characteristics of peptide binding (15)
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