B cell responses to a peptide epitope. I. The cellular basis for restricted recognition.
Primary humoral responses in BALB/c mice to a variety of peptide constructs containing a common 15-amino acid residue antigenic determinant (PS1) in conjunction with one or more Th cell epitopes were examined. In all cases, the mature IgG response was found to focus primarily on a tetrapeptide sequence, Asp-Pro-Ala-Phe. The dominance of this segment was independent of the position of the PS1 determinant in the peptide sequence and was also observed in constructs with a random secondary structure. In contrast to the mature IgG response, the early primary IgM response was constituted by multiple specificities that collectively spanned a major proportion of the PS1 sequence. However, subsequent progression of this response entailed a strict selection for only those Abs directed against the Asp-Pro-Ala-Phe segment and apparently occurred at or around the time of the IgM to IgG class switch. Studies of murine responses to peptide analogs containing single amino acid substitutions within the Asp-Pro-Ala-Phe sequence revealed that emergence of this segment as the dominant epitope was a consequence of active suppression of B cells directed against alternate determinants. Positive selection of this subset of Abs correlated with overall higher avidity for epitope binding and was the outcome of a competitive process enforced by the limiting amounts of Th cell help available in the early stages of the primary response.
Agarwal
A
A
International Center for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, India.
Sarkar
S
S
Nazabal
C
C
Balasundaram
G
G
Rao
K V
KV
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000918:Antibody Specificity; D001402:B-Lymphocytes / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology*; D005260:Female; D016056:Immunodominant Epitopes / Q000276:immunology; D017578:Immunoglobulin Class Switching; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000939:Epitopes; D016056:Immunodominant Epitopes; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D009842:Oligopeptides