HLA peptide length preferences control CD8+ T cell responses.
J Immunol
; 191(2): 561-71, 2013 Jul 15.
Article
em En
| MEDLINE
| ID: mdl-23749632
ABSTRACT
Class I HLAs generally present peptides of 8-10 aa in length, although it is unclear whether peptide length preferences are affected by HLA polymorphism. In this study, we investigated the CD8(+) T cell response to the BZLF1 Ag of EBV, which includes overlapping sequences of different size that nevertheless conform to the binding motif of the large and abundant HLA-B*44 supertype. Whereas HLA-B*1801(+) individuals responded strongly and exclusively to the octamer peptide (173)SELEIKRY(180), HLA-B*4403(+) individuals responded to the atypically large dodecamer peptide (169)EECDSELEIKRY(180), which encompasses the octamer peptide. Moreover, the octamer peptide bound more stably to HLA-B*1801 than did the dodecamer peptide, whereas, conversely, HLA-B*4403 bound only the longer peptide. Furthermore, crystal structures of these viral peptide-HLA complexes showed that the Ag-binding cleft of HLA-B*1801 was more ideally suited to bind shorter peptides, whereas HLA-B*4403 exhibited characteristics that favored the presentation of longer peptides. Mass spectrometric identification of > 1000 naturally presented ligands revealed that HLA-B*1801 was more biased toward presenting shorter peptides than was HLA-B*4403. Collectively, these data highlight a mechanism through which polymorphism within an HLA class I supertype can diversify determinant selection and immune responses by varying peptide length preferences.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
/
Linfócitos T CD8-Positivos
/
Antígeno HLA-B18
/
Antígeno HLA-B44
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Austrália