Cryptic B cell determinant in a short peptide: T cells do not induce antibody response of B cells when their determinants entirely overlap each other.

A synthetic peptide fragment encompassing residues 21-40 (F21-40) of bovine beta-lactoglobulin was used as a model antigen to investigate the relationship between T and B cell determinants. The establishment of fine specificity for these determinants in F21-40 in BALB/c mice revealed that this short peptide contained two T cell determinants, Td1 (residues 21-32) and Td2 (28-40), and that Td2 entirely overlapped the dominant B cell determinant (Bd) of residues 28-40. A truncated peptide, F25-40, was capable of strongly restimulating F21-40-primed T cells in vitro, and its binding affinity to anti-F21-40 antibodies was the same as that of F21-40, indicating that F25-40 maintained the same antigenic structure as that of region 25-40 in F21-40. However, immunization with F25-40 could not elicit specific antibodies despite priming specific T cells. From these results, Bd in F25-40 can be regarded as a cryptic B cell determinant. The absence of antibody response to F25-40 was probably caused by the complete overlapping of Td2 and Bd. This overlapping may have caused the presentation of Td2 only by professional antigen-presenting cells, but never by Bd-specific B cells possessing the potential to be differentiated to antibody-producing cells by T cell help. These findings demonstrate that the co-existence of T and B cell determinants within a single molecule does not always assure specific antibody production, which depends upon the spatial relationship between these determinants.