Interaction of the Pertussis Toxin Peptide Containing Residues 30-42 with DR1 and the T-Cell Receptors of 12 Human T-Cell Clones

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 89; no. 7; pp. 2990 - 2994
• Main Authors: De Magistris, Maria Teresa, Di Tommaso, Annalisa, Domenighini, Mario, Censini, Stefano, Tagliabue, Aldo, Oksenberg, Jorge R., Steinman, Lawrence, Judd, Amrit K., O'Sullivan, Deirdre, Rappuoli, Rino
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01.04.1992; National Acad Sciences; National Academy of Sciences
• Subjects: Amino Acid Sequence; Amino acids; Antigen-antibody reactions, antigen-antibody complexes, antibody-complement and others. Study of affinity. Antigen presentation; Base Sequence; Binding Sites; Biological and medical sciences; Clone Cells; Disease; Epitopes; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; HLA-DR1 Antigen - immunology; Humans; Immunity (Disease); In Vitro Techniques; Medical research; Models, Molecular; Molecular immunology; Molecular interactions; Molecular Sequence Data; Molecules; Oligodeoxyribonucleotides - chemistry; Peptides - chemistry; Peptides - immunology; Pertussis Toxin; Protein Binding; Receptors, Antigen, T-Cell - immunology; Receptors, Antigen, T-Cell, alpha-beta - genetics; Receptors, Antigen, T-Cell, alpha-beta - immunology; Social interaction; T cell antigen receptors; T lymphocytes; Toxins; Vaccination; Virulence Factors, Bordetella - chemistry; Virulence Factors, Bordetella - immunology; Whooping cough; Human; T cell receptor; Antigenic determinant; Major histocompatibility system; Variable region; Class II histocompatibility antigen; Molecular interaction; Islet activating protein; Immunogenicity; Structure activity relation; Peptide fragment; T-Lymphocyte; Gene rearrangement; Recognition
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.89.7.2990

The interaction of the immunodominant pertussis toxin peptide containing residues 30-42 (p30-42) with soluble DR1 molecules and the T-cell receptor (TCR) of 12 DR1-restricted human T-cell clones has been analyzed. Peptide analogues of p30-42 containing single alanine substitutions were used in DR1-binding and T-cell proliferation assays to identify the major histocompatibility complex and TCR contact residues. Each T-cell clone was found to recognize p30-42 with a different fine specificity. However, a common core comprising amino acids 33-39 was found to be important for stimulation of all T-cell clones. Within this core two residues, Leu33and Leu36, interact with the DR1 molecule, whereas Asp34, His35, Thr37, and Arg39are important for TCR recognition in most of the clones. Computer modeling of the structure of p30-42 showed that an α-helical conformation is compatible with the experimental data. The analysis of TCR rearrangement revealed that the peptide was recognized by T-cell clones expressing different variable region α (Vα) and variable region β (Vβ) chains, although a preferential use of Vα8-Vβ13 and Vα11-Vβ 18 combinations was found in clones from the same donor. Understanding the details of the interaction of antigenic peptides with the major histocompatibility complex and TCR molecules should provide the theoretical basis to design T-cell epitopes and obtain more immunogenic vaccines.