Conformational restraints and flexibility of 14-meric peptides in complex with HLA-B*3501.
J Immunol
; 173(9): 5610-6, 2004 Nov 01.
Article
en En
| MEDLINE
| ID: mdl-15494511
ABSTRACT
Human HLA-B*3501 binds an antigenic peptide of 14-aa length derived from an alternative reading frame of M-CSF with high affinity. Due to its extraordinary length, the exact HLA binding mode was unpredictable. The crystal structure of HLA-B*3501 at 1.5 A shows that the N and C termini of the peptide are embedded in the A and F pockets, respectively, similar to a peptide of normal length. The central part of the 14-meric peptide bulges flexibly out of the groove. Two variants of the alternative reading frame of M-CSF peptide substituted at P2 or P2 and P9 with Ala display weak or no T cell activation. Their structure differs mainly in flexibility and conformation from the agonistic peptide. Moreover, the variants induce subtle changes of MHC alpha-helical regions implicated as critical for TCR contact. The TCR specifically recognizing this peptide/MHC complex exhibits CDR3 length within the normal range, suggesting major conformational adaptations of this receptor upon peptide/MHC binding. Thus, the potential antigenic repertoire recognizable by CTLs is larger than currently thought.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fragmentos de Péptidos
/
Antígeno HLA-B35
/
Factor Estimulante de Colonias de Macrófagos
/
Presentación de Antígeno
Límite:
Humans
Idioma:
En
Revista:
J Immunol
Año:
2004
Tipo del documento:
Article
País de afiliación:
Alemania