Amino Acid Residues That Flank Core Peptide Epitopes and the Extracellular Domains of CD4 Modulate Differential Signaling Through the T Cell Receptor

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 1994 Jun 1

PMID 7515103

Citations 24

Authors

D A Vignali

J L Strominger

Affiliations

Soon will be listed here.

Abstract

Hen egg lysozyme 52-61-specific CD4+ T cells responded by interleukin 2 (IL-2) secretion to any peptide containing this epitope regardless of length of NH2- and COOH-terminal composition. However, CD4- variants could only respond to peptides containing the two COOH-terminal tryptophans at positions 62 and 63. Substitutions at these positions defined patterns of reactivity that were specific for individual T cells inferring a T cell receptor (TCR)-based phenomenon. Thus, the fine specificity of major histocompatibility complex (MHC)-peptide recognition by the TCR was dramatically affected by CD4 and the COOH-terminal peptide composition. Peptides that failed to induce IL-2 secretion in the CD4- variants nevertheless induced strong tyrosine phosphorylation of CD3 zeta. Thus, whereas the TCR still recognized and bound to the MHC class II-peptide complex resulting in protein phosphorylation, this interaction failed to induce effective signal transduction manifested by IL-2 secretion. This provides a clear example of differential signaling mediated by peptides known to be naturally processed. In addition, the external domains of CD4, rather than its cytoplasmic tail, were critical in aiding TCR recognition of all peptides derived from a single epitope. These data suggest that the nested flanking residues, which are present on MHC class II but not class I bound peptides, are functionally relevant.

Citing Articles

Rapid viscoelastic changes are a hallmark of early leukocyte activation.

Zak A, Merino-Cortes S, Sadoun A, Mustapha F, Babataheri A, Dogniaux S Biophys J. 2021; 120(9):1692-1704.

PMID: 33730552 PMC: 8204340. DOI: 10.1016/j.bpj.2021.02.042.

Human leukocyte antigen (HLA) class II peptide flanking residues tune the immunogenicity of a human tumor-derived epitope.

MacLachlan B, Dolton G, Papakyriakou A, Greenshields-Watson A, Mason G, Schauenburg A J Biol Chem. 2019; 294(52):20246-20258.

PMID: 31619516 PMC: 6937582. DOI: 10.1074/jbc.RA119.009437.

Phosphoinositides regulate the TCR/CD3 complex membrane dynamics and activation.

Chouaki Benmansour N, Ruminski K, Sartre A, Phelipot M, Salles A, Bergot E Sci Rep. 2018; 8(1):4966.

PMID: 29563576 PMC: 5862878. DOI: 10.1038/s41598-018-23109-8.

Association of the porcine cluster of differentiation 4 gene with T lymphocyte subpopulations and its expression in immune tissues.

Xu J, Liu Y, Fu W, Wang J, Wang W, Wang H Asian-Australas J Anim Sci. 2014; 26(4):463-9.

PMID: 25049810 PMC: 4093383. DOI: 10.5713/ajas.2012.12576.

Barcoding T cell calcium response diversity with methods for automated and accurate analysis of cell signals (MAAACS).

Salles A, Billaudeau C, Serge A, Bernard A, Phelipot M, Bertaux N PLoS Comput Biol. 2013; 9(9):e1003245.

PMID: 24086124 PMC: 3784497. DOI: 10.1371/journal.pcbi.1003245.

References

Dianzani U, Shaw A, al-Ramadi B, Kubo R, Janeway Jr C . Physical association of CD4 with the T cell receptor. J Immunol. 1992; 148(3):678-88. View

Jorgensen J, Esser U, Fazekas de St Groth B, Reay P, Davis M . Mapping T-cell receptor-peptide contacts by variant peptide immunization of single-chain transgenics. Nature. 1992; 355(6357):224-30. DOI: 10.1038/355224a0. View

Rotzschke O, Falk K . Naturally-occurring peptide antigens derived from the MHC class-I-restricted processing pathway. Immunol Today. 1991; 12(12):447-55. DOI: 10.1016/0167-5699(91)90018-O. View

De Magistris M, Alexander J, Coggeshall M, Altman A, Gaeta F, Grey H . Antigen analog-major histocompatibility complexes act as antagonists of the T cell receptor. Cell. 1992; 68(4):625-34. DOI: 10.1016/0092-8674(92)90139-4. View

Ratcliffe M, Coggeshall K, Newell M, Julius M . T cell receptor aggregation, but not dimerization, induces increased cytosolic calcium concentrations and reveals a lack of stable association between CD4 and the T cell receptor. J Immunol. 1992; 148(6):1643-51. View

Collins T, Uniyal S, Shin J, Strominger J, Mittler R, Burakoff S . p56lck association with CD4 is required for the interaction between CD4 and the TCR/CD3 complex and for optimal antigen stimulation. J Immunol. 1992; 148(7):2159-62. View

LEAHY D, Axel R, Hendrickson W . Crystal structure of a soluble form of the human T cell coreceptor CD8 at 2.6 A resolution. Cell. 1992; 68(6):1145-62. DOI: 10.1016/0092-8674(92)90085-q. View

Vignali D, Moreno J, Schiller D, Hammerling G . Species-specific binding of CD4 to the beta 2 domain of major histocompatibility complex class II molecules. J Exp Med. 1992; 175(4):925-32. PMC: 2119163. DOI: 10.1084/jem.175.4.925. View

De Magistris M, Di Tommaso A, Domenighini M, Censini S, Tagliabue A, Oksenberg J . Interaction of the pertussis toxin peptide containing residues 30-42 with DR1 and the T-cell receptors of 12 human T-cell clones. Proc Natl Acad Sci U S A. 1992; 89(7):2990-4. PMC: 48789. DOI: 10.1073/pnas.89.7.2990. View

10.

Weber S, Traunecker A, Oliveri F, GERHARD W, Karjalainen K . Specific low-affinity recognition of major histocompatibility complex plus peptide by soluble T-cell receptor. Nature. 1992; 356(6372):793-6. DOI: 10.1038/356793a0. View

11.

Molina T, Kishihara K, Siderovski D, van Ewijk W, Narendran A, Timms E . Profound block in thymocyte development in mice lacking p56lck. Nature. 1992; 357(6374):161-4. DOI: 10.1038/357161a0. View

12.

Janeway Jr C . The T cell receptor as a multicomponent signalling machine: CD4/CD8 coreceptors and CD45 in T cell activation. Annu Rev Immunol. 1992; 10:645-74. DOI: 10.1146/annurev.iy.10.040192.003241. View

13.

Hunt D, Michel H, Dickinson T, Shabanowitz J, Cox A, Sakaguchi K . Peptides presented to the immune system by the murine class II major histocompatibility complex molecule I-Ad. Science. 1992; 256(5065):1817-20. DOI: 10.1126/science.1319610. View

14.

Frank S, Cenciarelli C, Niklinska B, Letourneur F, Ashwell J, Weissman A . Mutagenesis of T cell antigen receptor zeta chain tyrosine residues. Effects on tyrosine phosphorylation and lymphokine production. J Biol Chem. 1992; 267(19):13656-60. View

15.

Vignali D, Moreno J, Schiller D, Hammerling G . Does CD4 help to maintain the fidelity of T cell receptor specificity?. Int Immunol. 1992; 4(5):621-6. DOI: 10.1093/intimm/4.5.621. View

16.

Reay P, Wettstein D, Davis M . pH dependence and exchange of high and low responder peptides binding to a class II MHC molecule. EMBO J. 1992; 11(8):2829-39. PMC: 556762. DOI: 10.1002/j.1460-2075.1992.tb05350.x. View

17.

Haughn L, Gratton S, Caron L, Sekaly R, Veillette A, Julius M . Association of tyrosine kinase p56lck with CD4 inhibits the induction of growth through the alpha beta T-cell receptor. Nature. 1992; 358(6384):328-31. DOI: 10.1038/358328a0. View

18.

Nelson C, Roof R, McCourt D, UNANUE E . Identification of the naturally processed form of hen egg white lysozyme bound to the murine major histocompatibility complex class II molecule I-Ak. Proc Natl Acad Sci U S A. 1992; 89(16):7380-3. PMC: 49713. DOI: 10.1073/pnas.89.16.7380. View

19.

Fremont D, Matsumura M, Stura E, Peterson P, Wilson I . Crystal structures of two viral peptides in complex with murine MHC class I H-2Kb. Science. 1992; 257(5072):919-27. DOI: 10.1126/science.1323877. View

20.

Germain R, Hendrix L . MHC class II structure, occupancy and surface expression determined by post-endoplasmic reticulum antigen binding. Nature. 1991; 353(6340):134-9. DOI: 10.1038/353134a0. View