Primary Structure and MHC Restriction of Peptide-Defined T Cell Epitopes from Recombinant Mycobacterial Protein Antigens

Using the predictive algorithm of Rothbard and Taylor (1988. EMBO J. 7:93) and the primary structure of gp63 (Button, L., and M.R. McMaster. 1988. J. Exp. Med. 167:724; Miller, R.A., S.G. Reed, and M. Parsons. 1990. Mol. Biochem. Parasitol. 39:267) we have been able to delineate the structures of a number of gp63 T-cell epitopes which stimulate the proliferation of CD4+ cells. One of these synthetic antigens, inoculated subcutaneously with adjuvant, was shown to specifically induce proliferation of the Th1 subset and provided immunoprotection against two species of Leishmania parasites.

Download Full-text

Picroliv, the Iridoid Glycoside Fraction ofPicrorhiza Kurroa, Selectively Augments Human T cell Response to Mycobacterial Protein Antigens

Immunopharmacology and Immunotoxicology ◽

10.3109/08923979809031518 ◽

1998 ◽

Vol 20 (4) ◽

pp. 579-588 ◽

Cited By ~ 7

Author(s):

Sudhir Sinha ◽

Jyoti Mehrotra ◽

Lakshmi Bala ◽

A. K. Jaiswal ◽

B. N. Dhawan

Keyword(s):

T Cell ◽

Cell Response ◽

Iridoid Glycoside ◽

T Cell Response ◽

Protein Antigens ◽

Human T Cell ◽

Mycobacterial Protein

Download Full-text

Enhancing immunogenicity by limiting susceptibility to lysosomal proteolysis

Journal of Experimental Medicine ◽

10.1084/jem.20052442 ◽

2006 ◽

Vol 203 (9) ◽

pp. 2049-2055 ◽

Cited By ~ 134

Author(s):

Lélia Delamarre ◽

Rachael Couture ◽

Ira Mellman ◽

E. Sergio Trombetta

Keyword(s):

T Cells ◽

T Cell ◽

Antibody Responses ◽

T Cell Epitopes ◽

Protein Antigens ◽

B Cell Epitopes ◽

Histocompatibility Complex ◽

Lysosomal Proteolysis ◽

Antigen Presenting

T cells recognize protein antigens as short peptides processed and displayed by antigen-presenting cells. However, the mechanism of peptide selection is incompletely understood, and, consequently, the differences in the immunogenicity of protein antigens remain largely unpredictable and difficult to manipulate. In this paper we show that the susceptibility of protein antigens to lysosomal proteolysis plays an important role in determining immunogenicity in vivo. We compared the immunogenicity of proteins with the same sequence (same T cell epitopes) and structure (same B cell epitopes) but with different susceptibilities to lysosomal proteolysis. After immunizing mice with each of the proteins adsorbed onto aluminum hydroxide as adjuvant, we measured serum IgG responses as a physiological measure of the antigen's ability to be presented on major histocompatibility complex class II molecules and to prime CD4+ T cells in vivo. For two unrelated model antigens (RNase and horseradish peroxidase), we found that only the less digestible forms were immunogenic, inducing far more efficient T cell priming and antibody responses. These findings suggest that stability to lysosomal proteolysis may be an important factor in determining immunogenicity, with potential implications for vaccine design.

Download Full-text

Type II and III Receptors for Immunoglobulin G (IgG) Control the Presentation of Different T Cell Epitopes from Single IgG-complexed Antigens

Journal of Experimental Medicine ◽

10.1084/jem.187.4.505 ◽

1998 ◽

Vol 187 (4) ◽

pp. 505-515 ◽

Cited By ~ 60

Author(s):

Sebastian Amigorena ◽

Danielle Lankar ◽

Volker Briken ◽

Laurent Gapin ◽

Mireille Viguier ◽

...

Keyword(s):

T Cell ◽

T Lymphocytes ◽

Mhc Class Ii ◽

Cytoplasmic Tail ◽

Class Ii ◽

T Cell Epitopes ◽

Protein Antigens ◽

B Lymphoma Cells ◽

Antigen Presenting ◽

Selection Of

T cell receptors on CD4+ lymphocytes recognize antigen-derived peptides presented by major histocompatibility complex (MHC) class II molecules. A very limited set of peptides among those that may potentially bind MHC class II is actually presented to T lymphocytes. We here examine the role of two receptors mediating antigen internalization by antigen presenting cells, type IIb2 and type III receptors for IgG (FcγRIIb2 and FcγRIII, respectively), in the selection of peptides for presentation to T lymphocytes. B lymphoma cells expressing recombinant FcγRIIb2 or FcγRIII were used to assess the presentation of several epitopes from two different antigens. 4 out of the 11 epitopes tested were efficiently presented after antigen internalization through FcγRIIb2 and FcγRIII. In contrast, the 7 other epitopes were efficiently presented only when antigens were internalized through FcγRIII, but not through FcγRIIb2. The capacity to present these latter epitopes was transferred to a tail-less FcγRIIb2 by addition of the FcγRIII-associated γ chain cytoplasmic tail. Mutation of a single leucine residue at position 35 of the γ chain cytoplasmic tail resulted in the selective loss of presentation of these epitopes. Therefore, the nature of the receptor that mediates internalization determines the selection of epitopes presented to T lymphocytes within single protein antigens.

Download Full-text

Integral use of immunopeptidomics and immunoinformatics for the characterization of antigen presentation and rational identification of BoLA-DR-presented peptides and epitopes

10.1101/2020.12.14.422738 ◽

2020 ◽

Author(s):

Andressa Fisch ◽

Birkir Reynisson ◽

Lindert Benedictus ◽

Annalisa Nicastri ◽

Deepali Vasoya ◽

...

Keyword(s):

T Cell ◽

Antigen Presentation ◽

Integrated Approach ◽

Class Ii ◽

T Cell Epitopes ◽

Protein Antigens ◽

Binding Motifs ◽

Leukocyte Antigen ◽

High Level

Major histocompatibility complex (MHC) peptide binding and presentation is the most selective event defining the landscape of T cell epitopes. Consequently, understanding the diversity of MHC alleles in a given population and the parameters that define the set of ligands that can be bound and presented by each of these alleles (the immunopeptidome) has an enormous impact on our capacity to predict and manipulate the potential of protein antigens to elicit functional T cell responses. Liquid chromatography-mass spectrometry (LC-MS) analysis of MHC eluted ligands (EL data) has proven to be a powerful technique for identifying such peptidomes, and methods integrating such data for prediction of antigen presentation have reached a high level of accuracy for both MHC class I and class II. Here, we demonstrate how these techniques and prediction methods can be readily extended to the bovine leukocyte antigen class II DR locus (BoLA-DR). BoLA-DR binding motifs were characterized by EL data derived from cell lines expressing a range of DRB3 alleles prevalent in Holstein-Friesian populations. The model generated (NetBoLAIIpan - available as a web-server at www.cbs.dtu.dk/services/NetBoLAIIpan ) was shown to have unprecedented predictive power to identify known BoLA-DR restricted CD4 epitopes. In summary, the results demonstrate the power of an integrated approach combining advanced MS peptidomics with immunoinformatics for characterization of the BoLA-DR antigen presentation system and provide a novel tool that can be utilised to assist in rational evaluation and selection of bovine CD4 T cell epitopes.

Download Full-text

Mechanisms influencing the immunodominance of T cell determinants.

Journal of Experimental Medicine ◽

10.1084/jem.168.6.2091 ◽

1988 ◽

Vol 168 (6) ◽

pp. 2091-2104 ◽

Cited By ~ 152

Author(s):

L Adorini ◽

E Appella ◽

G Doria ◽

Z A Nagy

Keyword(s):

T Cell ◽

Antigen Processing ◽

Cell Epitope ◽

Class Ii ◽

Amino Acid Sequences ◽

Foreign Protein ◽

T Cell Epitopes ◽

Protein Antigens ◽

Cell Repertoire

The preferential recognition of certain amino acid sequences from foreign protein antigens by T cells is referred to as T cell epitope immunodominance. To determine the mechanisms underlying this phenomenon, we have studied the correlation between the interaction of a series of synthetic peptides encompassing the entire hen egg-white lysozyme (HEL) sequence with class II molecules of the H-2k haplotype, and T cell responsiveness to these peptides. After HEL priming, three immunodominant T cell epitopes were found: two, included in the HEL sequences 51-61 and 112-129, were recognized in association with I-Ak molecules, and one, included in sequence 1-18, in association with I-Ek molecules. Accordingly, these peptides bound to the appropriate class II molecule, as demonstrated by competition for antigen presentation. Several other HEL peptides, although capable of associating with class II molecules, were not immunodominant. The absence of immunodominance has been shown to arise by three different mechanisms: (a) competition by an immunodominant peptide for presentation in vivo, (b) failure to generate the peptide during antigen processing, and (c) an inherently poor capacity of the T cell repertoire to respond to a particular peptide-MHC complex.

Download Full-text