HLA micropolymorphisms strongly affect peptide-MHC multimer-based monitoring of antigen-specific CD8+ T cell responses.
J Immunol
; 192(2): 641-8, 2014 Jan 15.
Article
en En
| MEDLINE
| ID: mdl-24342804
ABSTRACT
Peptide-MHC (pMHC) multimers have become one of the most widely used tools to measure Ag-specific T cell responses in humans. With the aim of understanding the requirements for pMHC-based personalized immunomonitoring, in which individuals expressing subtypes of the commonly studied HLA alleles are encountered, we assessed how the ability to detect Ag-specific T cells for a given peptide is affected by micropolymorphic differences between HLA subtypes. First, analysis of a set of 10 HLA-A*0201-restricted T cell clones demonstrated that staining with pMHC multimers of seven distinct subtypes of the HLA-A*02 allele group was highly variable and not predicted by sequence homology. Second, to analyze the effect of minor sequence variation in a clinical setting, we screened tumor-infiltrating lymphocytes of an HLA-A*0206 melanoma patient with either subtype-matched or HLA-A*0201 multimers loaded with 145 different melanoma-associated Ags. This revealed that of the four HLA-A*0206-restricted melanoma-associated T cell responses observed in this patient, two responses were underestimated and one was overlooked when using subtype-mismatched pMHC multimer collections. To our knowledge, these data provide the first demonstration of the strong effect of minor sequence variation on pMHC-based personalized immunomonitoring, and they provide tools to prevent this issue for common variants within the HLA-A*02 allele group.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Péptidos
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Polimorfismo Genético
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Antígeno HLA-A2
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Linfocitos T CD8-positivos
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Complejo Mayor de Histocompatibilidad
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Antígenos de Neoplasias
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
J Immunol
Año:
2014
Tipo del documento:
Article