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Updated: Aug 6, 2026

Immunopeptidomics: Isolation of Mouse and Human MHC Class I- and II-Associated Peptides for Mass Spectrometry Analysis
Published on: October 15, 2021
Epitopes of the class I major histocompatibility complex (MHC-I) recognized in the syngeneic or allogeneic context
1INSERM U602, Microenvironnement et Physiopathologie de la Differenciation, Hôpital Paul Brousse, 94800 Villejuif, France.
Class 1 major histocompatibility complex (MHC-I)-antigenic peptide exposed at the target cell surface is crucial for the adaptive immune response exerted in the self/syngeneic context by cytotoxic T lymphocyte (CTL). Such a complex also provides epitopes in the allogeneic context for antibody response directed against the MHC-I polymorphic determinant. In the present report we examined the formation of the MHC-I-peptide complex leading predominantly to the expression of T and/or B cell epitopes in a process of internal versus external antigenic peptide loading onto the binding groove of MHC-I. Analyses using antibodies specific to complex MHC-I-peptide generated in the syngeneic context to mimic T cell receptor (TCR) in comparison with antibodies specific to the MHC-I polymorphic determinant allowed the observation that the external peptide loading to MHC-I, while remaining necessary for inducing the formation of B cell epitopes, was less efficient than the internal one for generating T cell epitopes. Thus, external loading of peptide to the MHC-I appeared to match more closely the allogeneic situation and the humoral immunity in general, while internal peptide loading corresponded with the self/syngeneic context of the cellular CTL response.
Class 1 major histocompatibility complex (MHC-I)-antigenic peptide exposed at the target cell surface is crucial for the adaptive immune response exerted in the self/syngeneic context by cytotoxic T lymphocyte (CTL). Such a complex also provides epitopes in the allogeneic context for antibody response directed against the MHC-I polymorphic determinant. In the present report we examined the formation of the MHC-I-peptide complex leading predominantly to the expression of T and/or B cell epitopes in a process of internal versus external antigenic peptide loading onto the binding groove of MHC-I. Analyses using antibodies specific to complex MHC-I-peptide generated in the syngeneic context to mimic T cell receptor (TCR) in comparison with antibodies specific to the MHC-I polymorphic determinant allowed the observation that the external peptide loading to MHC-I, while remaining necessary for inducing the formation of B cell epitopes, was less efficient than the internal one for generating T cell epitopes. Thus, external loading of peptide to the MHC-I appeared to match more closely the allogeneic situation and the humoral immunity in general, while internal peptide loading corresponded with the self/syngeneic context of the cellular CTL response.
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