This lesson is only available in Korean for now.
Prof. Kwon's Antigen Presentation, First Steps

How a cell shows
what is inside it

To spot an infected cell the immune system must look inside it. But the membrane is opaque.
The answer was a noticeboard โ€” a cell chops up its own proteins and hangs the fragments on its surface. These 20 lessons follow how that board is built, why it differs between people, and how cancer takes it down.
Not just in words: from 30,000 IMGT/HLA alleles and IEDB mass-spectrometry peptides you draw the polymorphism map yourself, find the binding motifs, build a predictor by hand and score it on a different experiment. Python runs right inside this page.

๐ŸŽซ MHC๐Ÿงฌ HLA polymorphism๐Ÿ“Š PSSM ๐ŸŽฏ neoantigens๐Ÿ Python๐Ÿ”ฌ IEDBยทIMGTยทTCGA๐Ÿ‡ฌ๐Ÿ‡ง English
Start lesson 1 โ†’

How you'll learn

๐Ÿ”ฌWith real data

Not a simulation. Alleles are counted from the IMGT/HLA file itself; 32,000 mass-spec-confirmed 9mers are pulled from IEDB's 9.2 GB peptide file; mutations come from 10,443 TCGA samples.

๐ŸงญA function map without the structure

In lesson 8 you stack 5,880 HLA-A sequences and count position by position. The positions that come out โ€” 9, 62, 97, 114, 116, 152 โ€” are exactly the published binding pockets. Without ever looking at a structure.

๐Ÿ“Change the ruler, change the answer

Two rulers on the same data give two different pictures. Change the anchor threshold and the anchors change; change the gene list and the 'defect rate' moves tenfold. The moment you fix a criterion you have fixed the answer.

โœ๏ธWrite down what you couldn't do

We did not count LOH, did not ship other populations' frequencies, could not adjust for TMB. Lesson 20 splits what this data supports from what it does not in a table โ€” that habit is the point of the course.

Full curriculum

01
๊ฒŒ์‹œํŒ์˜ ๋ฐœ๋ช… โ€” ์„ธํฌ๊ฐ€ ์†์„ ๋‚ด๋ณด์ด๋Š” ์ด์œ 
T์„ธํฌ๋Š” ๊ป์งˆ๋งŒ ๋งŒ์งˆ ์ˆ˜ ์žˆ๋‹ค ยท ์ด 20๊ฐ•์ด ํ‘ธ๋Š” ๋ฌธ์ œ
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02
MHC-I ์˜ ๊ตฌ์กฐ โ€” ์–‘๋์ด ๋ง‰ํžŒ ํ™ˆ
์™œ ํ•˜ํ•„ 8~11 ๊ธ€์ž์ธ๊ฐ€ ยท ์ ‘์‹œ์˜ ๋ชจ์–‘์ด ์ •ํ•˜๋Š” ๊ฒƒ
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03
ใ€์‹ค์Šตใ€‘ ํŽฉํƒ€์ด๋“œ ํ‘œ๋ฅผ ์—ฐ๋‹ค โ€” ๋ฌด์—‡์ด ์‹ค๋ ค ์žˆ๋‚˜
IEDB ์กฐ๊ฐ ์ฝ๋Š” ๋ฒ• ยท ๋‘ ๊ฐ€์ง€ ์‹คํ—˜์ด ๋œปํ•˜๋Š” ๊ฒƒ
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04
ํ”„๋กœํ…Œ์•„์ข€ โ€” ์“ฐ๋ ˆ๊ธฐ ์ฒ˜๋ฆฌ์žฅ์ด ์ •๋ณด์›์ด ๋˜๋‹ค
๋‹จ๋ฐฑ์งˆ์„ ์ž๋ฅด๋Š” ํ†ต ยท ๊ทธ๋ฆฌ๊ณ  ๋ฉด์—ญํ”„๋กœํ…Œ์•„์ข€์œผ๋กœ ๊ฐˆ์•„ ๋ผ์šฐ๊ธฐ
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05
TAP ๊ณผ ์ ์žฌ ๋ณตํ•ฉ์ฒด โ€” ์กฐ๊ฐ์„ ์ ‘์‹œ๊นŒ์ง€ ๋‚˜๋ฅธ๋‹ค
๋ง‰ ํ•˜๋‚˜๋ฅผ ๊ฑด๋„ˆ๋Š” ์ผ ยท ๊ทธ๋ฆฌ๊ณ  ๋ฐ”์ด๋Ÿฌ์Šค๊ฐ€ ์—ฌ๊ธฐ๋ฅผ ๋…ธ๋ฆฌ๋Š” ์ด์œ 
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06
MHC-II ์™€ ๊ต์ฐจ์ œ์‹œ โ€” ๋ฐ–์—์„œ ์ฃผ์šด ๊ฒƒ์„ ๋ณด์—ฌ ์ค€๋‹ค
๋‘ ๋ฒˆ์งธ ๊ฒŒ์‹œํŒ ยท ๊ทธ๋ฆฌ๊ณ  ๊ทœ์น™์„ ๊นจ๋Š” ๋ฐ˜์น™ ํ•˜๋‚˜
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07
HLA ๋‹คํ˜•์„ฑ โ€” ์‚ฌ๋žŒ๋งˆ๋‹ค ๋‹ค๋ฅธ ๊ฒŒ์‹œํŒ
์‚ฌ๋žŒ ์œ ์ „์ฒด์—์„œ ๊ฐ€์žฅ ๋‹ค์–‘ํ•œ ์ž๋ฆฌ ยท ์™œ ๊ทธ๋ ‡๊ฒŒ๊นŒ์ง€ ๋‹ค์–‘ํ•œ๊ฐ€
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08
ใ€์‹ค์Šตใ€‘ ๋‹คํ˜•์„ฑ ์ง€๋„ โ€” ์–ด๋А ์ž๋ฆฌ๊ฐ€ ์‚ฌ๋žŒ๋งˆ๋‹ค ๋‹ค๋ฅธ๊ฐ€
341 ์ž๋ฆฌ๋ฅผ ๋‘ ๊ฐ€์ง€ ์ž๋กœ ์žฌ ๋ณธ๋‹ค ยท ๊ทธ๋ฆฌ๊ณ  ๊ทธ ๋‹ต์ด ๋†€๋ž๋‹ค
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09
ใ€์‹ค์Šตใ€‘ ๊ฒฐํ•ฉ ๋ชจํ‹ฐํ”„ โ€” ๊ฒŒ์‹œํŒ๋งˆ๋‹ค ์ข‹์•„ํ•˜๋Š” ๊ธ€์ž๊ฐ€ ๋‹ค๋ฅด๋‹ค
IEDB ์งˆ๋Ÿ‰๋ถ„์„ ํŽฉํƒ€์ด๋“œ 4,000๊ฐœ ร— ๋Œ€๋ฆฝ์œ ์ „์ž 8๊ฐœ ยท ์•ต์ปค๋ฅผ ๋ˆˆ์œผ๋กœ ์ฐพ๋Š”๋‹ค
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10
ใ€์‹ค์Šตใ€‘ ์˜ˆ์ธก๊ธฐ๋ฅผ ์ง์ ‘ ๋งŒ๋“ ๋‹ค โ€” ์—ด ์ค„์งœ๋ฆฌ PSSM
๋ชจํ‹ฐํ”„๋กœ ๋ฐฐ์šฐ๊ณ  ๋‹ค๋ฅธ ์‹คํ—˜์œผ๋กœ ์ฑ„์ ํ•œ๋‹ค ยท AUC 0.75~0.87
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11
์‹ ์ƒํ•ญ์› โ€” ์•”์„ธํฌ๋งŒ ๊ฐ€์ง„ ๊ฒŒ์‹œ๋ฌผ
๋Œ์—ฐ๋ณ€์ด๊ฐ€ ๋งŒ๋“œ๋Š” '๋‚ด ๋ชธ์— ์—†๋˜' ์กฐ๊ฐ ยท ์™œ ๋ฉด์—ญ์น˜๋ฃŒ๊ฐ€ ์—ฌ๊ธฐ์— ๊ฑธ๋ ค ์žˆ๋‚˜
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12
ใ€์‹ค์Šตใ€‘ KRAS G12C ๋ฅผ ๊ฒŒ์‹œํŒ์— ์˜ฌ๋ ค ๋ณธ๋‹ค
๋ณ€์ด ํ•˜๋‚˜ โ†’ 9mer ์•„ํ™‰ ๊ฐœ โ†’ ์—ฌ๋Ÿ ๊ฒŒ์‹œํŒ ์ฑ„์  ยท ๋ˆ„๊ฐ€ ๋ณผ ์ˆ˜ ์žˆ๋‚˜
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13
๊ฒฐํ•ฉ โ‰  ์ œ์‹œ โ‰  ๋ฉด์—ญ์›์„ฑ โ€” ์‚ฌ์Šฌ์„ ์„ผ๋‹ค
์˜ˆ์ธก๋œ ๊ฒฐํ•ฉ์ฒด ์ค‘ ์‹ค์ œ๋กœ T์„ธํฌ๋ฅผ ๊นจ์šฐ๋Š” ๊ฒƒ์€ ๋ช‡ %์ธ๊ฐ€
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14
๋ฉด์—ญํŽฉํ‹ฐ๋” โ€” ๊ฒŒ์‹œํŒ์„ ํ†ต์งธ๋กœ ์ฝ๋Š”๋‹ค
์งˆ๋Ÿ‰๋ถ„์„์œผ๋กœ MHC ์—์„œ ์กฐ๊ฐ์„ ๋–ผ์–ด ๋‚ธ๋‹ค ยท ๋ฌด์—‡์ด ๋ณด์ด๊ณ  ๋ฌด์—‡์ด ์•ˆ ๋ณด์ด๋‚˜
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15
ํ•ญ์›์ œ์‹œ ๊ณ ์žฅ โ€” ์•”์ด ๊ฒŒ์‹œํŒ์„ ๋‚ด๋ฆฌ๋Š” ๋ฒ•
B2M ยท HLA ยท TAP ยท ์ธํ„ฐํŽ˜๋ก  ๊ฒฝ๋กœ ยท ๋ฉด์—ญ์น˜๋ฃŒ๊ฐ€ ์•ˆ ๋“ฃ๋Š” ๊ฐ€์žฅ ํ”ํ•œ ์ด์œ 
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16
ใ€์‹ค์Šตใ€‘ TCGA ์—์„œ ํ•ญ์›์ œ์‹œ ๊ณ ์žฅ์„ ์„ผ๋‹ค
๋ฌด์—‡์„ ์…Œ๊ณ  ยท ๋ฌด์—‡์„ ๋ชป ์…Œ๋Š”์ง€๊นŒ์ง€ ์ ๋Š”๋‹ค
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17
ใ€์‹ค์Šตใ€‘ ๋ˆ„๊ฐ€ ์ด ๊ฒŒ์‹œํŒ์„ ๊ฐ€์กŒ๋‚˜ โ€” HLA ๋นˆ๋„์™€ ํ˜•ํ‰์„ฑ
์—ฌ๋Ÿ ๋Œ€๋ฆฝ์œ ์ „์ž๋กœ ๋ช‡ %๋ฅผ ๋ฎ๋‚˜ ยท ๊ทธ๋ฆฌ๊ณ  ๋ˆ„๊ตฌ์˜ ๋ช‡ %์ธ๊ฐ€
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18
ใ€์‹ค์Šตใ€‘ HLA ์™€ ์งˆ๋ณ‘ โ€” ์˜ค์ฆˆ๋น„๊ฐ€ ์ปค๋„ ๋ชป ์“ฐ๋Š” ์ด์œ 
๊ฐ•ํ•œ ์—ฐ๊ด€ โ‰  ์ข‹์€ ๊ฒ€์‚ฌ ยท ์œ ๋ณ‘๋ฅ ์ด ๋ชจ๋“  ๊ฒƒ์„ ๋ฐ”๊พผ๋‹ค
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19
ใ€์‹ค์Šตใ€‘ ๋…ผ๋ฌธ์ด ์“ด 49๊ฐœ ์œ ์ „์ž ํ•„ํ„ฐ๋ฅผ ๋‹ค์‹œ ๋งŒ๋“ ๋‹ค
DDX54 ๋…ผ๋ฌธ Fig 1B ์•ž์— ๋†“์ธ ์กฐ์šฉํ•œ ํ•œ ์ค„ ยท ์™œ ๊ทธ ์ค„์ด ๊ฒฐ๋ก ์„ ์ •ํ•˜๋‚˜
โœ“
20
์ •๋ฆฌ โ€” ๊ฒŒ์‹œํŒ์ด ์ •ํ•˜๋Š” ๊ฒƒ๊ณผ ์ •ํ•˜์ง€ ๋ชปํ•˜๋Š” ๊ฒƒ
20๊ฐ•์ด ๋‚จ๊ธด ๊ฒƒ ยท ๋งํ•  ์ˆ˜ ์žˆ๋Š” ๊ฒƒ๊ณผ ๋งํ•  ์ˆ˜ ์—†๋Š” ๊ฒƒ
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