Structural characteristics of an antigen required for its interaction with Ia and recognition by T cells

Sette, Alessandro; Buus, Søren; Colón, S M; Smith, John A.; Miles, Craig; Grey, Howard M.

doi:10.1038/328395a0

Cited by 369 publications

(212 citation statements)

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“…On the basis of statistical analysis it has been suggested that immunodominant sites in T cell stimulating peptides have a high conformational propensity [19] and several workers have proposed that the ability to form secondary structure is important for antigenicity [20][21][22][23][24][25][26]. In particular, Berzofsky and co-workers [27] have shown that 18 out of 22 known immunodominant helper T cell epitopes correspond to sequences that are predicted to form stable amphipathic helices.…”

Section: Resultsmentioning

confidence: 99%

Conformation of a T cell stimulating peptide in aqueous solution

et al. 1989

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Using two-dimensional NMR spectroscopy and circular dichroism spectroscopy it is demonstrated that a T cell stimulating peptide corresponding to residues 132-153 of sperm whale myoglobin populates helical conformations in aqueous solution. This finding is in accordance with proposals that immunodominant sites in T cell stimulating peptides have a high conformational propensity. The observation of secondary structure in aqueous solutions of this and other immunogenic peptides has important implications for initiation of protein folding.

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Section: Resultsmentioning

confidence: 99%

Conformation of a T cell stimulating peptide in aqueous solution

et al. 1989

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“…To this end, Troybodies were constructed that have V regions specific for class II molecules, and various model T cell epitopes in the constant part. As model T cell epitopes, the following were used: aa residues 91-101 from the mouse 2 315 Ig L chain (33), 323-339 OVA (27), 110 -120 HA (25), and 46 -61 HEL (26). The 2 315 epitope is presented on I-E d class II molecules to CD4 ϩ T cells (6,33), as is the HA epitope (36).…”

Section: Construction Of Mhc Class Ii-specific Troybodies With T Cellmentioning

confidence: 99%

Efficient Delivery of T Cell Epitopes to APC by Use of MHC Class II-Specific Troybodies

Lunde

Western

Rasmussen

et al. 2002

The Journal of Immunology

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A major objective in vaccine development is the design of reagents that give strong, specific T cell responses. We have constructed a series of rAb with specificity for MHC class II (I-E). Each has one of four different class II-restricted T cell epitopes genetically introduced into the first C domain of the H chain. These four epitopes are: 91–101 λ2315, which is presented by I-Ed; 110–120 hemagglutinin (I-Ed); 323–339 OVA (I-Ad); and 46–61 hen egg lysozyme (I-Ak). We denote such APC-specific, epitope-containing Ab “Troybodies.” When mixed with APC, all four class II-specific Troybodies were ∼1,000 times more efficient at inducing specific T cell activation in vitro compared with nontargeting peptide Ab. Furthermore, they were 1,000–10,000 times more efficient than synthetic peptide or native protein. Conventional intracellular processing of the Troybodies was required to load the epitopes onto MHC class II. Different types of professional APC, such as purified B cells, dendritic cells, and macrophages, were equally efficient at processing and presenting the Troybodies. In vivo, class II-specific Troybodies were at least 100 times more efficient at targeting APC and activating TCR-transgenic T cells than were the nontargeting peptide Ab. Furthermore, they were 100–100,000 times more efficient than synthetic peptide or native protein. The study shows that class II-specific Troybodies can deliver a variety of T cell epitopes to professional APC for efficient presentation, in vitro as well as in vivo. Thus, Troybodies may be useful as tools in vaccine development.

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“…Also, the association pattern of peptides to different allele variants of murine Ia is a reflection of the MHC restriction of the immune response [3,4]. Several workers have attempted to unravel the relevant struc-tural requirements of TD h peptides to interact with murine [5][6][7] or human [8 -14] class II molecules. The X-ray structure of a class II molecule [15] has confirmed that the groove is occupied by a single peptide, and also, that its structure is similar to the one found for class I molecules [16].…”

Section: Determinants Recognized By T-helper Cellsmentioning

confidence: 99%

Specific and general HLA-DR binding motifs: comparison of algorithms

et al. 2000

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Using panels of peptides well characterized for their ability to bind to HLA DR1, DRB1*1101, or DRB1*0401 molecules, algorithms were deduced to predict binding to these molecules. These algorithms consist of blocks of 8 amino acids containing an amino acid anchor (Tyr, Phe, Trp, Leu, Ile, or Val) at position i and different amino acid combinations at positions i؉2 to i؉7 depending on the class II molecule. The sensitivity (% of correctly predicted binder peptides) and specificity (% of correctly predicted non-binder peptides) of these algorithms, were tested against different independent panels of peptides and compared to other algorithms reported in the literature. Similarly, using a panel of 232 peptides able to bind to one or more HLA molecules as well as 43 non-binder peptides, we deduced a general motif for the prediction of binding to HLA-DR molecules. The sensitivity and specificity of this general motif was dependent on the threshold score used for the predictions. For a score of 0.1, the sensitivity and specificity were 84.7% and 69.8%, respectively. This motif was validated against several panels of binder and non-binder peptides reported in the literature, as well as against 35, 15-mer peptides from hepatitis C virus core protein, that were synthesized and tested in a binding assay against a panel of 19 HLA-DR molecules. The sensitivities and specificities against these panels of peptides were similar to those attained against the panels used to deduce the algorithm. These results show that comparison of binder and non-binder peptides, as well as correcting for the relative abundance of amino acids in proteins, is a useful approach to deduce performing algorithms to predict binding to HLA molecules.

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Structural characteristics of an antigen required for its interaction with Ia and recognition by T cells

Cited by 369 publications

References 0 publications

Conformation of a T cell stimulating peptide in aqueous solution

Conformation of a T cell stimulating peptide in aqueous solution

Efficient Delivery of T Cell Epitopes to APC by Use of MHC Class II-Specific Troybodies

Specific and general HLA-DR binding motifs: comparison of algorithms

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