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Modification of the Inhibitory Amino Acid for Epitope Peptide Binding onto Major Histocompatibility Complex Class II Molecules Enhances Immunogenicity of the Antigen
Author(s) -
Chang S.H.,
Kim J.,
Lee K.Y.,
Kim H.J.,
Chung Y. J.,
Park C. U.,
Kim B. S.,
Jang Y.S.
Publication year - 2004
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.0300-9475.2004.01364.x
Subject(s) - epitope , immunogenicity , antigen , major histocompatibility complex , immune system , biology , microbiology and biotechnology , t cell , antibody , arginine , antigen presentation , peptide , amino acid , chemistry , biochemistry , immunology
Previously, the arginine at hen egg‐white lysozyme 61 (HEL 61) was characterized as inhibiting T‐lymphocyte stimulation due to the inefficient binding of the arginine‐containing epitope peptide to the corresponding major histocompatibility complex class II molecules in C57BL/6 mice. In this study, we produced recombinant HEL, with arginine or alanine at HEL 61, and compared its ability to induce immune responses in mice to see whether modification of an inhibitory amino acid could enhance the immunogenicity of an inefficient antigen. Immunization of the mice with modified HEL induced strong antibody and T‐cell immune responses against the native antigen. The enhanced T‐cell immune response was due to a more specific elevation of the T‐cell responses to the HEL 46–61 epitope region than to other epitope regions, although recognition of the other epitope peptides of HEL was generally increased. Mass spectrometric analyses of the epitope peptides generated by splenic antigen‐presenting cells indicated that production of the epitope peptides encompassing HEL 46–61 was efficient using the modified antigen. These results suggest that modification of the critical amino acid residue(s) involved in hampering induction of an efficient immune response is an effective method to improve the immunogenicity of an inefficient antigen.