title: Administration of PLP139-151 primes T cells distinct from those spontaneously responsive in vitro to this antigen.
abstract: We examined the TCR repertoire used by naive SJL mice in their in vitro spontaneous response to proteolipid protein (PLP) 139-151 by Vbeta-Jbeta spectratyping and compared it to that used after immunization with the peptide. T cells from immunized mice use the public rearrangement Vbeta10-Jbeta1.1, but naive mice do not; in contrast, TCR CDR3-beta rearrangements of Vbeta18-Jbeta1.2 and Vbeta19-Jbeta1.2 consistently are associated with the spontaneous response. T cells involved in spontaneous and induced responses can each recognize PLP(139-151) presented in vivo, but its s.c. administration has different consequences for the two repertoires. Four days after immunization, T cells associated with spontaneous responsiveness appear in the draining lymph nodes but disappear by day 10 and never appear elsewhere. Simultaneously, Vbeta10-Jbeta1.1 T cells are likewise activated in the lymph nodes by day 4 and spread to the spleen by day 10. Eight- to 10-wk-old naive mice use a narrower repertoire of TCRs than do immunized age-matched mice. Induced Vbeta10-Jbeta1.1 T cells home to the CNS during experimental autoimmune encephalomyelitis, whereas we failed to detect Vbeta18-Jbeta1.2 and Vbeta19-Jbeta1.2 TCR rearrangements in the CNS. Thus, we observe that administration of PLP(139-151) primes a T cell repertoire distinct from the one responsible for spontaneous responsiveness. This "immunized" repertoire substitutes for the naive one and becomes dominant at the time of disease onset.
authors.affiliation: Institute of General Pathology, Catholic University, Rome, Italy.
authors.forename: Romina
authors.initials: R
authors.lastname: Penitente
authors.forename: Chiara
authors.initials: C
authors.lastname: Nicolò
authors.forename: Peter
authors.initials: P
authors.lastname: Van den Elzen
authors.forename: Gabriele
authors.initials: G
authors.lastname: Di Sante
authors.forename: Chiara
authors.initials: C
authors.lastname: Agrati
authors.forename: Francesca
authors.initials: F
authors.lastname: Aloisi
authors.forename: Eli E
authors.initials: EE
authors.lastname: Sercarz
authors.forename: Francesco
authors.initials: F
authors.lastname: Ria
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D005260:Female; D015329:Gene Rearrangement, T-Lymphocyte; D007108:Immune Tolerance; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D018991:Myelin Proteolipid Protein / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D001324:Autoantigens; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; C435023:myelin proteolipid protein (139-151)