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. 1992 Jan 1;89(1):416-20.
doi: 10.1073/pnas.89.1.416.

Tolerance to a self-protein involves its immunodominant but does not involve its subdominant determinants

R Cibotti  1 , J M Kanellopoulos, J P Cabaniols, O Halle-Panenko, K Kosmatopoulos, E Sercarz, P Kourilsky
Affiliations

Tolerance to a self-protein involves its immunodominant but does not involve its subdominant determinants

R Cibotti et al. Proc Natl Acad Sci U S A. .

Abstract

We have produced transgenic mice expression hen egg-white lysozyme (HEL) under the control of a ubiquitous promoter, so that in transgenic animals, HEL is presumably present in the serum and thymus throughout the period of establishment of the T-cell repertoire. We show that HEL transgenic H-2d mice with HEL blood levels greater than 10 ng/ml are tolerant to HEL as well as to the immunodominant peptide 108-116. Thus, their T lymphocytes do not proliferate in response to the immunodominant peptide 108-116 after in vivo immunization with HEL or peptide 108-116. In contrast, in transgenic mice tolerant to HEL, the state of tolerance to subdominant peptides 1-18 and 74-96 appears variable and highly depended on HEL blood levels. Complete unresponsiveness is seen when HEL serum levels are high, and this unresponsiveness is reached at a lower HEL concentration for peptide 1-18 than for peptide 74-96. Thus, a hierarchy exists among the three peptides (108-116 much greater than 1-18 greater than 74-96) for induction of a response to HEL and for HEL tolerance induction in T cells specific for these peptides. Persistence in the periphery of autoreactive T cells recognizing subdominant peptides of self-proteins, as shown in this transgenic model, indicates that self-tolerance is limited to a subset of dominant self-peptides and suggests a role for T lymphocytes specific for subdominant determinants in autoimmunity.

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