A possible immunodominant epitope recognized by murine T lymphocytes immune to different myoglobins.

165

authors request that the following correction be noted. Mutant 49 of the Tac receptor subunit in which Thr-85, Thr-86 were replaced by Ala-85, Gly-86 was also modified at the C terminus of the polypeptide chain. The oligonucleotide used in the mutation reaction apparently hybridized with the single-stranded template at the correct location surrounding Thr-85, Thr-86 and also at a site after the codon for Gln-202. As a consequence, the C-terminal region of the mutant 49 protein differed markedly from that of the native molecule. The mutant protein bound to affinity supports coupled with interleukin 2 and the anti-Tac monoclonal antibody, but was defective for expression on the cell surface. Examination of a new mutant of the Tac protein in which Thr-85 and Thr-86 were replaced by Ala and Gly, respectively, but in which the remaining sequence was identical to that of the native protein, indicates that this substitution has no effect on cell-surface expression. Moreover Correction. In the article "Helper T-cell antigenic site identification in the acquired immunodeficiency syndrome virus gp120 envelope protein and induction of immunity in mice to the native protein using a 16-residue synthetic peptide" by

supporting

confidence: 56%

Helper T-cell antigenic site identification in the acquired immunodeficiency syndrome virus gp120 envelope protein and induction of immunity in mice to the native protein using a 16-residue synthetic peptide.

Cease¹,

Margalit²,

Cornette³

et al. 1987

165

“…There is some tendency toward sites being in a-helical segments in the native structure, but it is not strong enough to explain the results. For myoglobin the known T-cell sites are in a-helical regions in the native molecule (23)(24)(25)(26)38). The same appears to be true for cytochrome c (39)-although end effects in this case make calculation of amphipathicity difficult and the utility of the concept doubtful.…”

Section: Discussionmentioning

confidence: 99%

“…1): from residues 59 to 81, from residues 104 to 114, and from residues 130 to 143. The latter two contain known T-cell immunodominant sites (23)(24)(25)(26); the antigenicity of the former is not known. Close to 50% of the residues in the myoglobin sequence were scored as 1, reflecting its high a-helical content.…”

Section: Methodsmentioning

confidence: 99%

T-cell antigenic sites tend to be amphipathic structures.

DeLisi¹,

Berzofsky²

1985

Self Cite

440

180

We propose, on the basis of physical chemical and biological requirements for T-cell activation by antigen, that sites on a protein that can stimulate T lymphocytes will be capable of forming a stable amphipathic structure (i.e., one with separated hydrophobic and hydrophilic surfaces), displaying periodicity in hydrophobic residues. A spectral analysis of the 12 antigenic sites to which the method could be applied indicates that the amphipathic periodicity hypothesis is valid for 10 of them, generally with reliabilities that are well above 98%, with periodicities compatible with an a-helical structure.An 11th case manifests a different type of amphipathicity. The analyses require only a knowledge of amino acid sequence. The finding that T-cell antigenic sites show a high correlation with amphipathicity greatly simplifies the search for such sites and is potentially important for vaccine development.The identification and analysis of antigenic sites on a protein and ultimately the ability to predict their location is central to a wide range of problems in fundamental and applied immunology. The molecular basis of antigen processing and recognition is an example of the former (1-3); vaccine development is an example of the latter (4). The emergence of hybridoma technology and the consequent availability of monoclonal antibodies have greatly facilitated the search for sites recognized by antibodies, and the antigenic architecture ofa number ofproteins has now been mapped in considerable detail (5). Careful examination of the data thus generated indicates that antigenic sites are generally located on the protein surface (5, 6) in regions of relatively high segmental flexibility (7,8) and hydrophilicity (9). The majority of the exposed surface may be antigenic for antibodies.In contrast to the information and emerging concepts on antibody antigenicity, data on antigenic sites recognized by T cells are scarce, and potentially predictive concepts are essentially nonexistent. The latter deficiency is to some extent related to the former, and both are linked to the relative complexity of the T-cell response. Unlike B-cell immunoglobulin, which can recognize native, solubilized antigen, recognition of antigen by T-cell receptors requires that it be proteolytically processed or otherwise unfolded by accessory cells, such as macrophages, B cells, or dendritic cells, and that the antigenic segments thus produced be presented to T cells on the surface of an accessory cell in association with a major transplantation antigen, such as the murine Ia or the human HLA-D region antigens (1,3,10,11). This complexity, coupled with the fact that the T-cell receptor has only recently become amenable to structural analysis, has also made determination of equilibrium constants for binding of free antigen to T-cell receptors difficult. Thus, quantitative studies of recognition by T-cell receptors, even at a phenomonological level, have progressed much more slowly than those for antibodies.Although the T-cell receptor-antigen syste...

“…Several recent findings could be interpreted as evidence that immune T cells see the primary structure of Ia or nominal antigen. The aforementioned studies of Hochman and Huber (16) (27), or insulin (28) suggested that Ia-restricted T cells see conformational determinants on nominal antigen. Taken together with the data presented here, we feel the evidence supports the conclusion that T cells recognize predominantly the conformation of Ia in both allogeneic and syngeneic responses.…”

Section: Discussionmentioning

confidence: 99%

The murine bm12 gene conversion provides evidence that T cells recognize predominantly Ia conformation.

Tse¹,

Kanamori²,

Walsh³

et al. 1985

The structure of the highly polymorphic Ia dimer is the genetically determined factor that controls the immune response to foreign antigens, albeit the mechanism remains unresolved. However, it is clear that, in diverse immune responses, effector T lymphocytes require recognition of self-Ia and foreign antigenic determinants on the surface of an antigen-presenting cell or an antibody-secreting B cell.