Linear epitopes of two different autoantigens (La/SSB and myelin basic protein) with a high degree of molecular similarity cause different humoral responses

Backgkround

Sequences 147–154aa of La/SSB and 139–146aa of human myelin basic protein (MBP) present 83% sequence similarity.

Objective

We investigated the immune response of both epitopes in rabbits and in sera from patients with autoimmune diseases.

Methods

Peptides 147–154aa of La/SSB and 139–146aa of MBP were used for immunizations of New Zealand White rabbits. Spreading to the other epitopes of La/SSB (289–308aa, 349–364aa) as well as the recombinant human MBP (hMBP) and La/SSB (recLa) was identified using ELISA assays. Sera from 49 patients with systemic lupus erythematosus (SLE), 44 patients with Sjögren's syndrome (pSS), and 18 with rheumatoid arthritis (RA) with anti-Ro\La reactivity were tested against the two peptides and the hMBP.

Results

Rabbits immunized with the La epitope developed early antibodies against all three La/SSB peptides, hMBP, and recLa. In contrast, rabbits immunized with the MBP peptide developed a late immune response to other La epitopes, hMBP, and recLa. Inhibition experiments using the MBP peptide as inhibitor against the hMBP showed that the 79% of reactivity was abolished, indicating that this peptide is the major antibody target in MBP. Twenty percent of pSS, 27% of SLE, and none from RA patients reacted with the 147–154aa La epitope; 28% of pSS, 22% of SLE, and 17% of RA sera reacted with the MBP peptide. Finally, 17% of pSS, 37% of SLE, and 30% of RA sera reacted with the hMBP.

Conclusion

La 147–154aa peptide when used for animal immunizations can induce immediate epitope spreading while the mimicking epitope MBP 139–146aa induces a delayed response against the other La epitopes. A significant proportion of human sera reacted with both peptides and hMBP. Thus, despite the fact that these two peptides present molecular similarity, they induce different immune responses.