Giao nhận kháng nguyên đến các thể nội bào sớm loại bỏ ưu thế của tế bào trình diện kháng nguyên BDCA3+ ở người trong việc trình diện chéo

Journal of Experimental Medicine - Tập 210 Số 5 - Trang 1049-1063 - 2013
Lillian B. Cohn1, Bithi Chatterjee1, Filipp Esselborn1, Anna Smed‐Sörensen1,2, Norihiro Nakamura1, Cécile Chalouni1, Byoung-Chul Lee1, Richard Vandlen1, Tibor Keler3, Peter Lauer4, Dirk G. Brockstedt4, Ira Mellman1, Lélia Delamarre1
1Genentech, South San Francisco, CA 94080 1
2Karolinska Institutet, 171 77 Solna, Sweden 2
3Celldex Therapeutics Inc., Phillipsburg, NJ 08865 3
4Aduro BioTech, Inc., Berkeley, CA 94710 4

Tóm tắt

Tế bào trình diện kháng nguyên BDCA3+ ở người (DCs), được coi là tương đương với tế bào CD8α+ ở chuột, được cho là có khả năng trình diện kháng nguyên trên các phân tử MHC lớp I (MHCI) hiệu quả hơn so với các quần thể DC khác. Nếu đúng như vậy, vẫn chưa rõ điều này có phản ánh sự chuyên biệt cho việc trình diện chéo hay là khả năng tổng quát được nâng cao trong việc trình diện kháng nguyên trên MHCI. Chúng tôi đã so sánh khả năng trình diện của tế bào BDCA3+ với tế bào BDCA1+ bằng một phương pháp định lượng trong đó các kháng nguyên được định hướng đến các khoang nội bào khác nhau thông qua việc nội hóa có trung gian thụ thể. Như mong đợi, tế bào BDCA3+ tỏ ra vượt trội trong việc trình diện chéo các kháng nguyên được cung cấp đến các thể nội bào muộn và lysosome thông qua việc tiếp nhận kháng thể chống DEC205 liên hợp với kháng nguyên. Sự khác biệt này có thể phản ánh hiệu quả lớn hơn trong việc kháng nguyên thoát khỏi lysosome của tế bào BDCA3+. Ngược lại, nếu các kháng nguyên được chuyển đến các thể nội bào sớm thông qua CD40 hoặc CD11c, tế bào BDCA1+ hoạt động hiệu quả trong việc trình diện chéo như tế bào BDCA3+. Vì tế bào BDCA3+ và BDCA1+ cũng tương đương trong việc trình diện các peptide và kháng nguyên tổng hợp nội sinh, tế bào BDCA3+ không có khả năng có cơ chế trình diện chéo cụ thể cho phân nhóm này. Do đó, nhiều quần thể DC có thể cũng hiệu quả trong việc trình diện các kháng nguyên ngoại lai cho tế bào T CD8+ miễn là kháng nguyên được giao đến các khoang nội bào sớm.

Từ khóa


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