Abstract
NZB mice spontaneously develop autoimmune haemolytic anaemia (AIHA) due to a T help er-dependent autoantibody response against the erythrocyte anion channel protein, Band 3. Here, we characterize the recognition of the Band 3 sequence 861-874, which carries the dominant, I-E-d-restricted T cell epitope. The ability of N and C-terminal truncated versions of peptide 861-874 to elicit NZB splenic T-cell proliferation indicated that the core epitope spans residues 862-870. Next, a set of alanine substitution analogues was tested to determine which residues functioned either as MHC anchor or TCR contact residues. A combination of proliferation and MHC:peptide binding assays identified residues 862(L), 864(V), 865(L), and 869(K) as I-E-d anchor residues, and 868(V) as the only TCR contact residue. The ability of the wild-type sequence 861-874 to compete with a high affinity reference peptide for binding to I-E-d indicates that the escape of pathogenic NZB T cells from purging of the autoreactive repertoire cannot be attributed to ineffective presentation of peptide 861-874 by its restricting element. It will now be possible to design altered peptide ligands of Band 3 861-874, in order to further dissect the mechanisms responsible for the maintenance and loss of T cell tolerance to RBC autoantigens, and to modulate the immune response in AIHA. (C) 2002 Elsevier Science Ltd.
Original language | English |
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Pages (from-to) | 149-157 |
Number of pages | 8 |
Journal | Journal of Autoimmunity |
Volume | 18 |
Issue number | 2 |
DOIs | |
Publication status | Published - 2002 |
Keywords
- auto-reactive T cells
- epitope
- NZB mouse
- autoimmune haemolytic anaemia
- Band 3
- CLASS-II MOLECULES
- PEPTIDE BINDING
- ENCEPHALOMYELITIS
- MHC
- ANTIGEN
- MICE
- AUTOANTIBODIES
- REPERTOIRE
- TOLERANCE
- RECEPTOR