Peptide binding and editing: generation of TCR ligands.
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Antigen Presentation↗
Biomedical subjects
L Adorini
Publications and source records attributed to L Adorini.
Pathogenic and protective T-cell responses in autoimmune diseases.
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Animals↗
Monoclonal suppressor T-cell factor displaying V H restriction and fine antigenic specificity.
The production of stable T-cell clones is essential for the study of T-cell-derived, specific immunoregulatory products and of specific T-cell receptors. T-cell clones have been established by radiation leukaemia virus (RadLV)-induced transformation of suppressor T lymphocytes specific for hen egg white lysozyme (HEL). We report here that culture supernatant obtained from these T-cell clones can, when injected into mice, specifically suppress the anti-HEL antibody response. This monoclonal T-cell product suppresses the antibody response induced by HEL and human lysozyme, but not that induced by ring-necked pheasant egg white lysozyme (REL), thus displaying fine antigenic specificity probably restricted to an epitope involving phenylalanine at amino acid residue 3, present in the N-terminal region of HEL and shared by human lysozyme but absent in REL. The suppression induced by this monoclonal T-cell product is restricted by both H-2 and Igh-1 genes whereas anti-HEL antibodies bearing a predominant idiotype are induced in all mice strains tested, irrespective of their H-2 haplotype or Igh-1 allotype.
Animals↗
Electron microscopic observations on T and B lymphocytes from spleens of syngeneic radiation chimaeras.
The ultrastructure of T and B lymphocytes has been examined in long-term syngeneic chimaeras and age-control mice. Spleen cell suspensions from these mice were passed through glass wool columns to obtain pure lymphocyte populations. These cells were then separated into T and B lymphocytes by nylon wool columns, and their purity was tested by cytotoxicity assays with anti-phi serum. Electron microscopic observations on such separated T and B lymphocytes did not reveal morphological differences except when the cells were fully differentiated, either as mature (T2) cells or plasmacells. In particular, T2 cells showed a very high cytoplasmic density, attributable to the presence of a larger number of microfilaments with respect to immature (T1) cells. In long-term chimaeras a significantly larger number of T2 cells was found as compared to age-control mice, and this morphological observation is correlated with the differences in immune reactivity and leukemia incidence previously described in these mice.
Age Factors↗
The presentation of antigen by MHC class II molecules.
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Animals↗
Partial overlap of Ir gene-controlled responses to two proteins of limited relatedness: hen egg-white lysozyme and human lysozyme.
The plaque-forming cell (PFC) response to human lysozyme (HUL) is regulated by an Ir gene(s) located within the major histocompatibility complex of the mouse. Mice of H-2a, H-2k, H-2v and H-2r haplotypes respond to HUL, whereas mice with H-2b, H-2d, H-2q, H-2s and H-2u haplotypes fail to generate substantial anti-HUL PFC responses. In contrast, only mice carrying the H-2b and H-2s haplotypes are non-responders to the distantly related hen eggwhite lysozyme (HEL). The major genetic control of the anti-HUL PFC response maps to the I-A subregion of the H-2 complex with perhaps a minor influence by a gene mapping to the right of the I-B subregion. HUL and HEL induce a cross-reactive suppressor cell, directed against a particular determinant found on both lysozymes. Once generated, these antigen-specific suppressor cells can affect the in vitro primary response to either lysozyme conjugated to sheep red blood cells. Despite this overlap, the strain distribution pattern of responsiveness is different for the two lysozymes. In the discussion, this was attributed to the MHC-related failure to process and/or present HEL to the HEL/HUL cross-reactive suppressor T cell in H-2q, d and u strains.
Animals↗
Selective inhibition of T cell responses by protein and peptide-based immunotherapy.
Recent progress in understanding antigen presentation to T cells has permitted researchers to identify a number of suitable attack points for selective immunointervention aimed at inhibiting inappropriate T cell activation: major histocompatibility complex (MHC) molecules, T cell receptor (TCR), CD4/CD8, and other accessory molecules. This has fostered the development of a new generation of immunosuppressive agents potentially useful in the prevention and/or treatment of autoimmune diseases, and induction of selective immunosuppression is currently being attempted using monoclonal antibodies or synthetic peptides. The selective immunosuppression by proteins and peptides may be sub-divided into three major categories: i) passive treatments aimed at inhibiting T cell activation by blocking the MHC binding site to any antigenic peptide, including autoantigens; ii) treatments aimed at incapacitating the autoreactive T cells, either by administration of the candidate autoantigen as protein or peptides in tolerogenic form, or by TCR antagonists able to induce selective T cell anergy; and iii) vaccination-like treatments aimed at inducing or enhancing regulatory T cells able to control the activity of pathogenic, autoreactive T cell. It is hoped that some of these approaches may finally lead to effective treatments able to interfere with the induction and/or progression of human autoimmune diseases.
Animals↗