T cell recognition of the posttranslationally cleaved intersubunit region of influenza virus hemagglutinin.
The influenza virus hemagglutinin is synthesized as a single polypeptide chain, but upon maturation it will posttranslationally be modified by a host cell related trypsin-like enzyme. The enzymatic cleavage attacks the so-called intersubunit region of the molecule giving rise to covalently linked HA1 and HA2 subunits. An I-Ed-restricted T cell epitope was identified in the highly conserved intact intersubunit region of the influenza virus hemagglutinin. T cell recognition of a 25-mer synthetic peptide comprising the intact intersubunit region does not require further processing and the elimination of the intervening Arg residue coupling the fusion peptide to the C-terminal segment of HA1 does not abolish the T cell activating capacity. The fine specificity pattern of a T cell hybridoma similar to that of the polyclonal T cell response demonstrates that a single T cell receptor is able to recognize peptides of different sizes representing not only the uncleaved but also the cleaved form of this hemagglutinin region. Based on specificity studies the epitope was localized to the C-terminal 11 amino acids of the HA1 subunit. The cross-reactivity of peptide-primed T cells with influenza virus infected antigen-presenting cells shows that fragments comprising the identified epitope of the intersubunit region can be generated as a result of natural processing of the hemagglutinin molecule. As antigen-presenting cells are lacking the enzyme which is responsible for the posttranslational modification of newly synthesized hemagglutinin molecules, the role of immature viral proteins in immune recognition is discussed.
Rajnavölgyi
E
E
Department of Immunology, L. Eötvös University, Göd, Hungary.
Nagy
Z
Z
Kurucz
I
I
Gogolák
P
P
Tóth
G K
GK
Váradi
G
G
Penke
B
B
Tigyi
Z
Z
Hollósi
M
M
Gergely
J
J
D000595:Amino Acid Sequence; D000818:Animals; D018604:Epitope Mapping; D005260:Female; D006183:H-2 Antigens / Q000276:immunology; D006389:Hemagglutinins, Viral / Q000276:immunology* / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D009980:Influenza A virus / Q000276:immunology*; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009976:Orthomyxoviridae Infections / Q000276:immunology; D011480:Protease Inhibitors / Q000494:pharmacology; D011499:Protein Processing, Post-Translational; D013601:T-Lymphocytes / Q000276:immunology*; D014760:Viral Fusion Proteins / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology
D006183:H-2 Antigens; D006389:Hemagglutinins, Viral; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D007376:Interleukin-2; D011480:Protease Inhibitors; D014760:Viral Fusion Proteins; D014765:Viral Vaccines