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The epitope specificity of T-cell help to B cells and of surface immunoglobulin-mediated B-cell-binding of antigens usually involves topographically distinct antigenic determinants. The possibility of cross-recognition of the same peptide sequence by both T cells and antibodies has been a matter of conflicting opinions. We investigated this subject by detailed mapping of T- and B-cell epitopes within four immunogenic mycobacterial peptides. The identified core sequences of T- and B-cell epitopes showed different topology within each peptide: they were partially overlapping or adjacent in two P38-derived peptides, but entirely overlapping in two Pig-derived peptides. The critically important result using the two truncated peptides (P19/67-78 and P19/ 146-155) containing only the fully overlapping epitope cores was, that they retained full potency for inducing antibody responses. However, despite this desirable overlap of determinants, antipeptide sera failed to block the proliferation of corresponding T-cell hybridomas. We conclude, that our study, in contrast to previous findings, suggests that overlapping topology of T- and B-cell epitopes within synthetic peptides does not necessarily impair B-cell immunogenicity. [ABSTRACT FROM AUTHOR]

Previously we have identified an immunodominant, eight-residue, epitope core sequence (TAAGNVNI) from the 19 000 MW protein of Mycobacterium tuberculosis, which is recognized in the context of multiple H-2 I-A molecules. In this study, the role of residues flanking this T-cell epitope core was examined, using a series of 20 mer analogue peptides in which the native flanking residues were progressively replaced with L-alanine. Analogue peptides were tested for their capacity to stimulate a CD4+ 19000 MW protein-specific T-cell line, revealing that all but one N-terminal flanking residue could be replaced collectively by alanine without significant loss of stimulatory activity. However, clear H-2-associated differences in the requirement for flanking residues were demonstrated with peptide-specific T-cell hybridomas. In particular, H-2d-derived hybridomas were much more stringent in their requirement for flanking residues than were hybridomas. All polyalanine-substituted peptides bound I-Ab molecules, with affinities similar to the native unsubstituted peptide. In contrast, significantly reduced binding to I-Ad was observed with several analogue peptides, although without a clear relationship to the degree of substitution. Furthermore, in H-2b mice, neither immunogenicity nor cross-reactivity with the native peptide showed a clear inverse relationship with respect to the degree of alanine substitution. The results presented in this paper indicate that flanking residues can influence T-cell specificity and that these effects may be controlled by major histocompatibility complex (MHC) haplotype. [ABSTRACT FROM AUTHOR]

Protective immunity against infection with Mycobacterium tuberculosis is imparted by T cells rather than antibodies, but B cells can play a role as antigen-presenting cells and in granuloma formation. We re-evaluated the role of B cells in the course of tuberculous infection in μ-chain knock-out (Ig-) mice. Surprisingly, the organs of M. tuberculosis-infected Ig- mice were found to have three- to eight-fold elevated counts of viable bacilli compared with normal littermates at 3-6 weeks post-infection. Splenic interferon-gamma responses to whole antigen were unimpaired, whilst proliferation to certain mycobacterial peptides was found to be diminished. However, bacille Calmette-Guérin (BCG) vaccination significantly reduced the infection in Ig- mice. The mechanisms by which B cells can influence primary tuberculous infection need further study. [ABSTRACT FROM AUTHOR]

The 16-kD protein constituent of the Mycobacterium tuberculosis complex has been known mainly for its prominent serological immunogenicity and species specificity in tuberculous infection. In this study. we evaluated the T cell immune repertoire in 27 sensitized healthy subjects and 46 patients with active tuberculosis using 14 overlapping 20mer peptides spanning the entire sequence of this protein. Four of the tested peptides individually stimulated proliferation of blood mono- nuclear cells from more than 50% of healthy controls. Tuberculosis patients reacted to a narrower peptide range and with a 17-27% lower rate of responses to the four most immunogenic peptides, but these differences do not distinguish in any simple way between the T cell repertoire of patients and sensitized healthy subjects. The most immunogenic peptide (91-110) was recognized by 67% of healthy subjects and by 50% of tuberculosis patients. Importantly, several non-responders to this peptide were stimulated with the other three most permissive peptides with sequences of 111-130, 71-91 and 21-40, resulting in an overall response rate to at least one of these four peptides of 93% in healthy controls and 74% in tuberculosis patients. ln view of this additive effect between the most immunogenic peptides, their combined use may achieve sufficient sensitivity in a test aimed at the specific discrimination between infected and non-infected healthy subjects. The major interest in testing with these peptides rests in their species specificity. which is not achieved using purified protein derivative (PPD). [ABSTRACT FROM AUTHOR]