Cross-reactivity of T cell lines and clones to beta-lactam antibiotics.
To clarify on a molecular level the specific T cell response to haptens like penicillin G, we generated T cell lines and clones from penicillin-allergic patients. Two types of beta-lactam reactivity of T cells could be delineated: one group of patients showed a rather restricted specificity, as the penicillin-elicited T cell lines generated from such donors proliferated only to the stimulating penicillin, but not to other beta-lactam antibiotics nor to cephalosporines, even if the side chain was identical. This indicates that the penicilloyl structure together with the side chain was recognized by these T cells. The second group comprised patients with more broadly reactive T cells, as they were restimulated by penicillin G as well as by related penicillins like amoxicillin or ampicillin, but not cephalosporines. This indicates that the penicilloyl structure, a common motif of penicillins, was important for T cell recognition. Clones generated from a broadly reactive patient confirmed this heterogeneity, as either monospecific or broadly specific T cell clones could be identified. This broad or very restricted pattern of T cell reactivity was reflected in the use of TCR Vbeta-chains: while the broadly reactive T cell lines showed a heterogenous TCR usage, the highly restricted T cell lines showed an up-regulation of one TCR Vbeta-chain. Thus, our data suggest that the outgrowth of T cells bearing a certain TCR Vbeta may be a sign of a limited cross-reactivity.
Mauri-Hellweg
D
D
Institute of Immunology and Allergology, Inselspital, Bern, Switzerland.
Zanni
M
M
Frei
E
E
Bettens
F
F
Brander
C
C
Mauri
D
D
Padovan
E
E
Weltzien
H U
HU
Pichler
W J
WJ
D000900:Anti-Bacterial Agents / Q000276:immunology*; D001483:Base Sequence; D018550:Cephalosporin Resistance / Q000276:immunology; D003429:Cross Reactions; D006801:Humans; D007073:Immunoglobulin E / Q000032:analysis; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D010403:Penicillin Resistance / Q000276:immunology*; D010406:Penicillins / Q000276:immunology; D011852:Radioallergosorbent Test; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D047090:beta-Lactams
D000900:Anti-Bacterial Agents; D010406:Penicillins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D047090:beta-Lactams; D007073:Immunoglobulin E