ISSN:0883-0185    

DOI:10.3109/08830189009056614

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

ISSN:0883-0185    

DOI:10.3109/08830189009056615

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

Peptide binding and lymph node T cell activation studies have been used to characterize T cell recognition of an encephalitogenic T cell autoantigen from myelin basic protein in mice of the H-2uhaplotype. An important role for MHC class II molecules in“determinant selection”is revealed. Amino acids which determine interactions with either the restriction element of the major histocompatibility complex (MHC) or the encephalitogenic T cell receptor are defined. This information enables the design of peptides which bind MHC yet do not crossreact with the autoantigen. Two such peptides compete with the autoantigen for binding to the disease associated class II molecule and inhibit induction of experimental autoimmune encephalomyelitis in H-2umice. Prospects for peptide mediated therapy are discussed

ISSN:0883-0185    

DOI:10.3109/08830189009056616

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

A series of analogue peptides have been generated, using as a template the core region of the OVA 323-339 peptide identified as critical in determining binding to I-Ad. Several of these“core extended”peptides had increased affinities for the I-Admolecule compared to the native sequence, and were able to inhibit activation of an I-Ad-restricted T cell hybridomain vitro. The induction of a T cell proliferative response to a peptide antigen could be inhibited by co-administration of core-extended peptide with antigen in the same adjuvant emulsion. Furthermore, inhibition also occurred when the inhibitor molecule was delivered separately one day before immunization. Finally, the induction of the autoimmune disease, experimental allergic encephalomyelitis (EAE), in susceptible mice could be reduced by the administration of a core-extended peptide with high affinity for the appropriate class II molecule. These findings have implications for the use of MHC antagonists in the control and treatment of MHC-associated autoimmune conditions in humans.

ISSN:0883-0185    

DOI:10.3109/08830189009056617

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

The goal of vaccination is to induce a protective immune response without inducing the disease itself or other undesirable effects. In the past this was achieved by giving inactivated or attenuated pathogens, with notable success in some cases, but problems of safety, efficacy or production in others. A currently pursued alternative is the construction of synthetic peptide vaccines that contain pathogen-derived determinants able to induce an immune response both at the B and the T cell level. Because T cells recognize peptide fragments which are derived from the processing of soluble proteins [1], the technical problems of epitope conformation can be largely avoided in the design of synthetic T cell sites. However the constraints presented by the extensive polymorphism of MHC antigens on one hand [2], and the obligate interaction between the antigenic peptide and the MHC molecule on the other [3], create a problem for the immune system. When an antigenic determinant does not interact favorably with the MHC molecules possessed by a given individual, T cell clones specific for this particular combination of determinant and MHC molecules cannot be activated and therefore not all individuals will respond to any one antigenic determinant. Thus in order to develop a synthetic peptide vaccine applicable to an entire population, individuals with each MHC haplotype would have to be studied to ascertain which peptides they predominantly recognize as T cell determinants.In this review, through the work we have done on malaria sporozoite vaccine development, we should like to propose new strategies for identifying pathogen-derived sequences whose characteristics offer possible solutions to the problem of MHC restriction of the immune response for peptide vaccines.

ISSN:0883-0185    

DOI:10.3109/08830189009056618

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

Within the last 15 years, the pendulum of immune preoccupation has swung vigorously in the direction of the self. It is now commonplace to note that the T cell repertoire is acquired through a complex positive and negative selective process of recognition of self molecules in an MHC context. Accordingly, the repertoire“directed against foreign antigens”merely represents fortuitous cross-reactivity by the T cells selected by means of self-determinants.The definition of“self”protein or self-T cell determinant is not an unambiguous one. The most inclusive definition would enumerate all overlapping sequences of 15 amino acids of all proteins coded for by the DNA of the organism including any mutants. A clearly more restrictive definition would only include those proteins that have access to the immune system and the major histocompatibility complex (MHC). Still more restrictive is the idea of a“dominant self”that includes only those determinants which are easily processed and presented, and which can bind with high affinity to one of the MHC Class I and Class II molecules. An interesting issue which also must be discussed is the concept of the“immune self”[1] which includes idiopeptides from both B cell receptor and T cell receptor variable regions, and MHC peptides, as well as other non-variable components derived from the immune system. In this paper, we will address some issues relating to the interactions of self-determinants with the MHC and the induction of tolerance.

ISSN:0883-0185    

DOI:10.3109/08830189009056619

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

ISSN:0883-0185    

DOI:10.3109/08830189009056613

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor