Systematic identification of immunodominant CD4+ T cell responses to HpaA in Helicobacter pylori infected individuals.

// Jian Hu 1,2,* , Li Chen 3,4,* , Wuchen Yang 1,5 , Bin Li 3 , Heqiang Sun 3 , Shanshan Wei 1 , Yafei He 1 , Zhuo Zhao 3 , Shiming Yang 1 , Quanming Zou 3 , Weisan Chen 6 , Hong Guo 1 and Chao Wu 3 1 Department of Gastroenterology, The Second Affiliated Hospital, Third Military Medical University, Chongqing, PR China 2 Department of Intensive Care Unit, Chengdu Military General Hospital, Chengdu, PR China 3 National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, PR China 4 Department of Blood Transfusion, The Second Affiliated Hospital, Third Military Medical University, Chongqing, PR China 5 Department of Hematology, The Second Affiliated Hospital, Third Military Medical University, Chongqing, PR China 6 T cell Laboratory, La Trobe Institute for Molecular Science, School of Molecular Science, La Trobe University, Bundoora, Victoria, Australia * These authors have contributed equally to this work Correspondence to: Chao Wu, email: // Hong Guo, email: // Keywords : Helicobacter pylori ; HpaA; immunodominant epitope; HLA-DRB1*0901; Immunology and Microbiology Section; Immune response; Immunity Received : November 17, 2015 Accepted : June 29, 2016 Published : August 05, 2016 Abstract In mice, antigen-specific CD4 + T cell response is indispensible for the protective immunity against Helicobacter pylori ( H. pylori ). It has been demonstrated that neuraminyllactose-binding hemagglutinin (HpaA) immunization protected mice from H. pylori infection in a CD4 + T cell dependent manner. However, much remains unclear concerning the human CD4 + T cell responses to HpaA. We conducted a systematic study here to explore the immunodominant, HpaA-specific CD4 + T cell responses in H. pylori infected individuals. We found that HpaA-specific CD4 + T cell responses varied remarkably in their magnitude and had broad epitope-specificity. Importantly, the main responses focused on two regions: HpaA76-105 and HpaA130-159. The HLA-DRB1*0901 restricted HpaA142-159 specific CD4 + T cell response was the most immunodominant response at a population level. The immunodominant epitope HpaA142-159 was naturally presented and highly conserved. We also demonstrated that it was not the broad peptide specificity, but the strength of HpaA specific CD4 + T cell responses associated with gastric diseases potentially caused by H. pylori infection. Such investigation will aid development of novel vaccines against H. pylori infection.