RESUMEN
V beta 8 has been shown to be used in the majority of antigen specific T cell hybridomas restricted by I-Ad and I-Ed. The usage of V beta 8 in these T cell responses in vivo was confirmed as V beta 8 depleted BALB/c mice responded weakly to these I-Ad- and I-Ed-restricted antigens. We used this deletion assay to further examine if V beta 8 is similarly dominantly used in alloreactive T cell specific for I-Ad/Ed. The depletion of V beta 8-population in allogenic mice did not affect the alloreactive responses toward I-Ad/Ed. Although specific for the same MHC, there is no apparent overlap on the use of TCR V beta 8 between alloreactive T cells and antigen-specific T cells.
Asunto(s)
Antígenos de Histocompatibilidad Clase II/inmunología , Receptores de Antígenos de Linfocitos T alfa-beta/genética , Linfocitos T/inmunología , Secuencia de Aminoácidos , Animales , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C3H , Ratones Endogámicos C57BL , Datos de Secuencia MolecularRESUMEN
We have explored the possibility of using peptides derived from a major histocompatibility complex (MHC) class II (I-Ab) molecule to modulate I-Ab-restricted T cell responses. Six peptides spanning the polymorphic regions of I-Ab were analyzed for competitive binding to the I-Ab molecule, and for efficacies in blocking I-Ab-specific T cell response. Only PB1 (residues 75-91 of beta chain) bound the I-Ab molecule with high affinity. When these MHC-derived peptides were administered simultaneously with antigen, PB1 effectively inhibited I-Ab-restricted T cell responses as well as another peptide PB2 (residues 59-78 of beta chain). PB2 inhibited specific T cell response only when it was administered simultaneously with antigen. Since PB2 is a weak binder of I-Ab, an additional mechanism must account for its inhibitory activity. Both PB1 and PB2 peptides elicited specific T cell responses, indicating that these peptides were not tolerogenic in syngeneic mice. However, the induction of T cells in response to PB1 and PB2 did not increase reactivity to I-Ab. MHC class II-derived peptides thus can be used to regulate T cell responses without the risk of autoreactivity.
Asunto(s)
Antígenos de Histocompatibilidad Clase II/inmunología , Péptidos/inmunología , Linfocitos T/inmunología , Secuencia de Aminoácidos , Animales , Unión Competitiva , Tolerancia Inmunológica , Ratones , Ratones Endogámicos , Datos de Secuencia Molecular , Receptores de Antígenos de Linfocitos T/inmunologíaRESUMEN
The majority of T cell hybridomas produced in the BALB/c mouse in response to immunization with lambda repressor cI recognize a peptide fragment comprising of residues 12 to 26 (P12-26). Some other parts of the cI (P1-14, P33-48 and P73-88) are defective in generating T cell responses in the BALB/c mouse. P73-88 may be converted into a T cell determinant if a few more amino acid residues are included (P67-88). Together with P46-67 and P80-102, most peptides derived from cI were capable of eliciting T cell responses by themselves in BALB/c mouse. The mechanisms underlying the selection of P12-26 over the other epitopes when lambda repressor was used as immunogen were examined. The dominant response to P12-26 was attenuated by tolerizing with intravenous administration of P12-26. Under such treatment the T cell response to P12-26 was reduced by 80% but there was no enhancement on the responses toward other epitopes. The selection of P12-26 is, thus, unlikely to be due to a competition at the T cell level. It was also found that the dominance of P12-26 was not simply due to a higher affinity of P12-26 for major histocompatibility complex molecules. For example P12-26 binds better to I-Ad molecule than P80-102, but co-injection with equimole of P12-26 only slightly inhibited P80-102-induced T cell response. Instead, it required a few molar excess of P12-26 to effectively block the association of P80-102 with I-Ad molecules and to inhibit the T cell immunity to P80-102. Since epitopes such as P46-67, P67-88 and P80-102 were generated from lambda repressor cI at a lower molar basis than that of P12-26, it is suggested that the dominance of P12-26 was probably generated by such stoichiometry difference, in addition to the higher affinity of P12-26 for I-Ad molecules.