Tn Glycosylation of the MUC6 Protein Modulates Its Immunogenicity and Promotes the Induction of Th17-biased T Cell Responses

免疫系统 细胞生物学
作者
Teresa Freire,Richard Lo-Man,Sylvie Bay,Claude Leclerc
出处
期刊:Journal of Biological Chemistry [Elsevier BV]
卷期号:286 (10): 7797-7811 被引量:36
标识
DOI:10.1074/jbc.m110.209742
摘要

The Tn antigen (α-GalNAc-O-Ser/Thr) is one of the most specific human cancer-associated structures. This antigen, together with mucins, the major carriers of O-glycosylated tumor antigens in adenocarcinomas, are being evaluated as anti-cancer immunotherapeutic targets. In particular, the MUC6 protein, which is normally expressed only in gastric tissues, has been detected in intestinal, pulmonary, colorectal, and breast carcinomas. To develop anti-cancer vaccines based on the Tn antigen, we produced MUC6 proteins with different Tn density by using mixtures of recombinant ppGalNAc-T1, -T2, and -T7. The obtained glycoproteins were characterized and analyzed for their immunological properties, as compared with the non-glycosylated MUC6. We show that these various MUC6:Tn glycoproteins were well recognized by both MUC6 and Tn-specific antibodies. However, Tn glycosylation of the MUC6 protein strongly affected their immunogenicity by partially abrogating Th1 cell responses, and promoting IL-17 responses. Moreover, the non-glycosylated MUC6 was more efficiently presented than MUC6:Tn glycoproteins to specific T CD4+ hybridomas, suggesting that Tn glycosylation may affect MUC6 processing or MHC binding of the processed peptides. In conclusion, our results indicate that Tn glycosylation of the MUC6 protein strongly affects its B and T cell immunogenicity, and might favor immune escape of tumor cells.

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
jason0023完成签到,获得积分10
刚刚
失眠的狗发布了新的文献求助10
刚刚
孝铮完成签到 ,获得积分10
1秒前
执着的松鼠完成签到,获得积分20
1秒前
nicole关注了科研通微信公众号
1秒前
1秒前
2秒前
山楂完成签到,获得积分10
2秒前
3秒前
希望天下0贩的0应助王某采纳,获得10
3秒前
NPC-CBI完成签到,获得积分10
4秒前
wonder123发布了新的文献求助30
5秒前
vv完成签到,获得积分10
5秒前
5秒前
5秒前
畅快芾完成签到,获得积分10
5秒前
6秒前
Mo发布了新的文献求助50
7秒前
phoenix完成签到,获得积分10
7秒前
ding应助干净又晴采纳,获得10
8秒前
虚拟的怀绿完成签到,获得积分10
8秒前
krisliu完成签到,获得积分10
8秒前
舍予有服发布了新的文献求助10
10秒前
酷波er应助老迟到的梦旋采纳,获得10
10秒前
10秒前
畅快芾发布了新的文献求助10
11秒前
小周完成签到,获得积分10
13秒前
田様应助jiajia采纳,获得10
14秒前
Hello应助zjs采纳,获得10
15秒前
ttong发布了新的文献求助10
15秒前
15秒前
ablesic.rong完成签到,获得积分10
16秒前
sml发布了新的文献求助10
16秒前
cutey小鲸鱼完成签到,获得积分20
17秒前
you完成签到,获得积分10
18秒前
krisliu发布了新的文献求助10
19秒前
YJ888发布了新的文献求助10
20秒前
干净又晴发布了新的文献求助10
21秒前
21秒前
jason完成签到,获得积分20
22秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
‘Unruly’ Children: Historical Fieldnotes and Learning Morality in a Taiwan Village (New Departures in Anthropology) 400
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
基于可调谐半导体激光吸收光谱技术泄漏气体检测系统的研究 350
Robot-supported joining of reinforcement textiles with one-sided sewing heads 320
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3989550
求助须知:如何正确求助?哪些是违规求助? 3531774
关于积分的说明 11254747
捐赠科研通 3270278
什么是DOI,文献DOI怎么找? 1804966
邀请新用户注册赠送积分活动 882125
科研通“疑难数据库(出版商)”最低求助积分说明 809176